J. Org. Chem. 1989,54, 4914-4929
4914
Palladium-Catalyzed Oxidative Cyclization of 1,SDienes. Influence of Different Substitution Patterns on the Regio- and Stereochemistry of the Reaction Thomas Antonsson, Christina Moberg,* and Louise Tottie Department of Organic Chemistry, Royal Institute of Technology, S-10044 Stockholm, Sweden
Andreas Heumann* Universitg d'Aix-Marseille 111,IPSOI- U A 126, Centre de S a i n t - J h j m e , F-13013 Marseille, France
Received April 17, 1989 Oxidative cyclization of 1,5-dienes in acetic acid and in the presence of the Pd(I1) regenerating catalyst system
Pd(OAc)2/Mn02/p-benzoquinone has been shown to yield, depending on the structure of the 1,5-diene, acetoxyexomethylenecyclopentanes or acetoxyvinylcyclopentanes. 1,5-Dienes with substitutents in the 1-and/or 3-position show a high preference for formation of regioisomers obtained by acetate attack a t the sterically least hindered double bond, but the products are usually mixtures of diastereomeric cis and trans cyclopentanes. trans-l-Phenyl-1,5-hexadienes react with complete stereoselectivity to yield exomethylenecyclopentanes with a single configuration of the exocyclic double bond. The oxidative cyclization method is synthetically useful, affording a large variety of cyclopentane systems.
Introduction Mono- and bicyclic compounds are important substrates in organic and natural product chemistry, Due to their widespread occurrence in nature, cyclopentane derivatives have attracted much attention, and major efforts have been devoted to their synthesis.'V2 Particularly useful methods for the construction of five-membered carbocycles are based on cycloaddition3 and metal-catalyzed cyclization4 strategies. A powerful example combining these methods is the trimethylene methane (TMM) cycloaddition reacti~n.~ Another approach to cyclic systems consists of submitting suitable, nonconjugated dienes to palladium(11)-catalyzedoxidation reactions.6 One reaction which has been extensively studied is the palladium-mediated nucleophilic addition to norbornadiene' to yield organopalladium intramolecular coordination compounds? The desired organic products can be liberated via carbonylationg and reductive'O or oxidative" cleavage of the car(1) Paouette. Chem. 1984., -119. 1. ~~, ...., L. A. Ton. Curr. .. - - ,~
~
.
l
~
~
~~
~
~~
(2) Trost, B. M. Chem. SOC. Reu. 1982,141. (3) Reviews: Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1977,16,10. Pawda, A. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, 1984, Vol. 1 and 2. (4) Cf. some recent example with Fe: Takacs, J. M.; Anderson, L. G. J. Am. Chem. SOC. 1987, 109, 2200. Co: Magnus, P.; Principe, L. M.; Slater, M. J. J. Org. Chem. 1987,52,1483. Pd: Trost, B. M.; Rise, F. J. Am. Chem. SOC. 1987,109,3487. Trost, B. M.; Walchli, R. J. Am. Chem. SOC.1987,109,3487. Hegedus, L. A. Tetrahedron 1984,40,2415; Angew. Chem., Int. Ed. Engl. 1988,27, 1113. Oppolzer, W.; Gaudin, J. M. Helu. Chim. Acta 1987,70,1477. Abelman, M. M.; Oh, T.; Overman, L. E. J . Org. Chem. 1987,52,4130. Negishi, E.; Zhang, Y.; O'Connor, B. Tetrahedron Lett. 1988,29,2915. Larock, R. C.; Song, H.; Baker, B. E.; Gong, W. H. Ibid. 1988, 29, 2919. (5) Review: Trost, B. M. Angew. Chem.,Int. Ed. Engl. 1986,25, 1. Cf. also: Trost, B. M.; MacPherson, D. T. J.Am. Chem. SOC.1987,109,3483. (6) Henry, P. M. Palladium-Catalyzed Oxidation of Hydrocarbons: D. Reidel Publishing Co.: Dordrecht, Holland, 1980. (7) Green, M.; Hancock, R. I. J. Chem. SOC.A 1967,2054. Forsellini, E.; Bombieri, G.; Crociani, B.; Boschi, T. J.Chem. SOC.,Chem. Commun. 1970, 1203. Betts, S. J.; Haszeldine, R. N.; Parish, R. V. J. Chem. SOC. A 1971, 3699. Hughes, R. P.; Powell, J. J . Organomet. Chem. 1972,34, C51. Ban, E. M.; Hughes, R. P.; Powell, J. J. Organomet. Chem. 1974, Chem. 69, 455. Segnitz, A.; Bailey, P. M.; Maitlis, P. M. J. Chem. SOC., Commun. 1973,698. Segnitz, A,; Kelly, E.; Taylor, S. H.; Maitlis, P. M. J . Organornet. Chem. 1977, 124, 113. Pietropaolo, R.; Cusmano, F.; Rotondo, E.; Spadaro, A. J. Organomet. Chem. 1978, 155, 117. (8) Omae, I. Organometallic Intramolecular-Coordination Compounds; Elsevier Science Publishers: Amsterdam, 1986. (9) Stille, J. K.; Hines, L. F. J. Am. Chem. SOC. 1970,92, 1798. Hines, 1972, 94, 485. Anderson, C. B.; L. F.; Stille, J. K. J. Am. Chem. SOC. Markovic, R. J. Serb. Chem. SOC.1985, 50, 125.
0022-3263/89/1954-4914$01.50/0
bon-palladium bond. Although stoichiometric12J3with respect to palladium, these transformations have recently been applied to the synthesis of prostaglandine endoperoxide ana10gues.l~ The first observation of cyclopentane formation by palladium-catalyzed oxidative cyclization was described by Brewis and Hughes in 1965.15 In the presence of palladium(I1) phosphine complexes, carbon monoxide, and high-pressure conditions, various substituted cyclopentanes could be obtained from dienes such as 1,5-hexadiene. Extreme conditions and/or fairly low yields are characteristics of these early transf~rmations.'~J~1,5-Cyclooctadiene shows a particular behavior, and palladium(11)-mediatedcyclization takes place with lead tetraacetate as a reoxidant,18under photochemical condition^,'^ or with carbon monoxide and phosphine ligands.20 Examples involving palladium-promoted formation of cyclopentane derivatives from noncyclic dienes include cyclization of 1,6-diene~,~l intramolecular coupling of vinylic halides,np23 (10) Coulson, D. R. J . Am. Chem. SOC. 1969, 91, 200. Vedejs, E.; Salomon, M. F. J. Am. Chem. SOC.1970, 92, 6965. (11) CrO3-py: Vedejs, E.; Salomon, M. F.; Weeks, P. D. J. Organomet. Chem. 1972,40,221. Clz and Brz: Wong, P. K.; Stille, J. K. J. Organornet. Chem. 1974, 70,121. Py-m-ClC,HIC03H: Harvie, I. J.; McQuillin, F. J. J. Chem. Soc., Chem. Commun. 1976,369. CuBr,: Budnik, R. A.; Kochi, J. K. J . Organomet. Chem. 1976,116, C3. (12) We owe a lot of our knowledge concerning the formation and cleavage of the C-Pd bond to these palladation reactions with olefins like norbornadiene or 1,5-cyclooctadiene; cf. also: Flood, T. C. Top. Stereochem. 1981, 12, 37. (13) Catalytic conditions have been used in one case: Heumann, A.; Waegell, B. Nouu. J. Chim. 1977, I, 277. (14) Larock, R. C.; Leach, D. R.; Bjorge, S. M. Tetrahedron Lett. 1982, 23, 715; J. Org. Chem. 1986,51,5221. Larock, R. C.; Leach, D. R. J. Org. Chem. 1984,49, 2144. (15) Brewis, S.; Hughes, P. R. J. Chem. SOC.,Chem. Commun. 1965, 489; 1967, 71. Brewis, S.; Hughes, P. R. Am. Chem. SOC.,Diu. Petrol. Chem. Prep. 1969, 14, B10. (16) Formation of bicyclo[3.3.1]-3-nonen-9-onefrom 1,5-cycloChem. Commun. octadiene: Brewis, S.; Hughes, P. R. J. Chem. SOC., 1966, 6 . Brewis, S. Brit. 1.144.166; Chem. Abstr. 1971, 75, 118041r. (17) Formation of cyanobrendane derivatives from endo-5-vinylbicyclo[2.2.1]-2-hepteneand HCN Brown, E. S.; Rick, E. A. Abstr. Am. Chem. SOC.Pet. Diu. Chem. Repr. 1969,14, B29. (18) Henry, P. M.; Davies, M.; Ferguson, G.; Phillips, S.; Restivo, R. J. Chem. SOC.,Chem. Commun. 1974, 112. Chung, S.-K.; Scott, I. A. Tetrahedron Lett. 1975, 49. Chernyuk, K. Y.; Mel'nikova, V. I.; Pivnitskii, Zh. Org. Khim. 1982, 18, 577 (Engl. Ed. p 503). (19) Akbarzadeh, M.; Anderson, C. B. J . Organomet. Chem. 1980,197, c5. (20) Hemmer, H.; Rambaud, J.; Tkatchenko, I. J. Organomet. Chem. 1975, 97, C57.
0 1989 American Chemical Society
J. Org. Chem., Vol. 54,No. 20, 1989 4915
Palladium-Catalyzed Oxidative Cyclization Scheme I
60 *C
1
TsOH/hexane
'4
_PdClz/CuClz/HOAc
@ 18
168
15a
14 (>95)
19
cyclization of enol ethers,24and oxidative cyclization of 1 , 5 - d i e n e ~ . ~The ~ * synthesis ~~ of a number of mono-, bi-, and tricyclic systems has been realized in this way. However, most of these reactions are stoichiometric with respect to palladium. In those which are catalytic, the choice of the reoxidation system is important. The classical "Wackernn catalyst PdC12-CuC12 gives quite selective but not general results.% Using the three-component system Pd(II)/p-benzoquinone/Mn02, we obtained conditions for both selective and general cyclization of 175-dienes.%* We report in this paper full experimental details for the selective formation of substituted exomethylenecyclopentanes in oxidative cyclization reactions.
Results and Discussion Reactions. A great variety of "1,5-hexadienesn have been cyclized by means of P ~ ( O A C )In ~ .the presence of the palladium(0) reoxidation system benzoquinone/Mn02 (in some cases benzoquinone alone), the reaction is catalytic with respect to the noble metal catalyst (1-5 mol %). An important feature concerns the substitution pattern (21) Grigg, R.; Malone, J. F.;Mitchell, T. R. B.; Ramasubbu, A.; Scott, Perkin Trans. 1 1984,1745. Trost, B. M.; Burgess, R. M. J. Chem. SOC., Chem. Commun. 1985,1084. Grigg, R.; Stevenson, P.; K. J. Chem. SOC., Worakun, T. Tetrahedron 1988,44, 2033 and 2049. (22) Grigg, R.; Stevenson, P.; Worakum, T. J . Chem. SOC.,Chem. Commun. 1984, 1073; 1985,971. (23) Carbonylation-cyclization with 1,4- and 1,5-dienes: Negishi, E.; Miller, J. A. J.Am. Chem. SOC.1983,105,6761. Tour, J. A.; Negishi, E. J. Am. Chem. SOC.1985, 107,8929. (24) Ito, Y.; Aoyama, H.; Hirao, T.; Mochizuki, A.; Saegusa, T. J. Am. Chem. SOC. 1979,101,494. Ito, Y.; Aoyama, H.; Saegusa, T. J. Am. Chem. SOC. 1980, 102, 4519. Kende, A. S.; Roth, B.; Sanfilippo, P. J. J . Am. Chem. SOC. 1982, 104, 1784. Kende, A. S.; Roth, B.; Sanfilippo, P. J.; Blacklock, T. J. J . Am. Chem. SOC.1982,104,5808. Kende, A. S.;Sanfilippo, P. J. Synth. Commun. 1983,13, 715. Kende, A. s.; Battista, R. A.; Sandoval, S. B. Tetrahedron Lett. 1984, 25, 1341. Kende, A. S.; Wustrow, D. J. Tetrahedron Lett. 1985,26,5411. Torres, L. E.; Larson, G. L. Tetrahedron Lett. 1986,27,2223. Stille, J. K.; Tanaka, M. J.Am. Chem. SOC. 1987,109, 3785. (25) The triene myrcene can be considered as a vinyl-substituted 1,5-diene and cyclizations have been described Dunne, K.; McQuillin, F.J. J . Chem. SOC. C 1970,2196. Takahashi, M.; Suzuki, H.; Moro-oka, Y.; Ikawa, T . Chem. Lett. 1979,53. Takahashi, M.; Urata, H.; Suzuki, H.; Moro-oka, Y.; Ikawa, T . J. Organomet. Chem. 1984,266,327. (26) Adachi, N.; Kikukawa, K.; Takagi, M.; Matsuda, T. Bull. Chem. SOC.J p n . 1975, 48, 521. (27) Review: Tsuji, J. Synthesis 1984, 369. (28) (a) Heumann, A.; Reglier, M.; Waegell, B. Angew. Chem., Znt. Ed. Engl. 1979,18,866 and 867. (b) Heumann, A,; Reglier, M.; Waegell, B. Tetrahedron Lett. 1983,24, 1971. (29) Preliminary reports have appeared: Antonsson, T.;Moberg, C.; Heumann, A. Poster presented at the XI1 I.C.O.M.C., Vienna, Austria, September 8-13,1985 (p 51). Antonsson, T.; Heumann, A.; Moberg, C. J . Chem. SOC.,Chem. Commun. 1986,518. (30) Moberg, C.; Antonsson, T.; Tottie, L.; Heumann, A. Chern. Scr. 1987, 27, 507.
(ref 31 a )
H
13
on the diene; modification on both the saturated and unsaturated parts of the diene strongly influence the regioand diastereoselectivities of the cyclization reactions. Cyclization (Pd(OA~)~/p-benzoquinone/ Mn02 1/ 4/ 20, 5 mol % Pd) of 175-hexadiene(1) in acetic acid resulted in the formation of a 65/25/10 mixture of the unsaturated acetates 2, 3, and 4 in a total yield of 72% (Table I). Dienes with two chemically different olefinic groups underwent attack of acetate preferentially at the sterically less hindered site. From d,l-&methyl-l,5-hexadiene (5), five isomers (ratio 39/30/12/12/7) were obtained in a total yield of 49%. The three major isomers (81% of the mixture) were exomethylenecyclopentanes 6a and 6b and the rearranged compound 7, all obtained by acetate attack at C5 of the diene. The trans/& (6b/6a) ratio was 57/43. The two resulting isomers were thought to be the regioisomers 8a and 8b, the ratio of acetate attack of the two double bonds thus being ca. 81/19. The ratio of the two isomers of 8 could be estimated to 63/37, showing a larger discrimination between formation of these two diastereomers than of those of 6. It was not, however, possible to assign the stereochemistry of the individual isomers. The ratio of attack at the two double bonds of d,l-3phenyl-175-hexadiene(9) turned out to be considerably higher (97/3), affording 10 and 11 as major isomers and only a minor amount of the regioisomer 12 (total yield 62%). The diastereoselectivity of the reaction was similar to that found for 5, as shown by the formation of a 48/52 mixture of the trans and cis isomers of compound 10. The two diastereomers could, however, be separated by crystallization of the trans isomer or by preparative HPLC. In contrast to the reactions above, remarkably high diastereoselectivity was observed upon cyclization of cis1,2-divinylcyclohexane (13), which yielded (1R*,6S*,7S*)-7-acetoxy-9-methylenebicyclo[ 4.3.01nonane (14) as the sole product (70%, Table I). The stereoselectivity of the reaction was verified by allowing the product to undergo base-catalyzed hydrolysis to afford 15a, followed by the M i t s ~ n o b reaction u ~ ~ ~ to yield the endo isomer 16a, which could be shown to be absent in the cyclization reaction mixture (Scheme I). Likewise, in the cyclization of d,l-1,2-divinylcyclohexane(17) only the (lS*,6S*,7S*)diastereoisomer (18) was formed, along with the isomerized compound 19 (total yield 54%, ratio 87/13) and two unidentified acetates (lo%, Table I). Both the cis- and trans-acetoxyindan derivatives 14 and 18 could easily be isomerized (TsOH, hexane, 60 "C) to the same (31) (a) Mitsunobu, 0. Synthesis 1981,l. (b) Another procedure could also be used for the inversion: Kaulen, J. Angew. Chem.,Znt. Ed. Engl. 1987, 26, 773.
Antonsson e t al.
J. Org. Chem., Vol. 54, No. 20,1989
4916
1,5-diene
Table I. Cyclization of 1,5-Dienes cyclized products regioisomer (normalized yields, %) ratio
yields of cyclized products: %
&
diastereomer ratio
other acetates (yields, % )
72
1
& 4\
2 (65)
3(25) 4(10)
49
A 5
6
6a(cis.30) 6b (trans, 39)
2
6: 57/43 8: 63/37
9713
48/52
e(cisandtrans, 7and 12)
7(12)
62
81/19
P
h
4
\
9 Ph
Ph
100 (cis.45) 10b (trans.42)
70
n 13
12 ( 3 )
11 (10)
aAC
>99/1
14 0 9 5 )
Ck
-
54 N
O
A
C
84/16
two other acetates (10)
>99/1
AcO-ph
@OAC
17
Ph
33
20
OAC
4
22 ( 4 ) + t w o other acetates (11)
Ph
21
@APh
OAC
17
79/21
21 (21)
I
9,
23
Ph
2 4 (79)
>99/1 Ph
26 - 2 9 53 55 59-64
-
34 OA c
RO A
Ph
C
30-33 d.Table I1 65-73)
34*
27
...%..
Me 0 ‘
Ph
ah
318 ( 1 2 ) OAc
36
k
35
4
LPh
O
Ph
>99/1
50150
>99/ 1
38: 74/26 30: 85/15
>99/1
not determined
3 6 (38)
31b (50) OAc I
37 38a
+b
(61)
bh
30s + b (391
2
41
OAC
39 HO
A= 40
L
O
A
41 (10)
.
Ph
J. Org. Chem., Vol. 54, No. 20, 1989 4917
Palladium-Catalyzed Oxidative Cyclization
Table I (Continued) cyclized products regioisomer (normalized yields, % 1 ratio
yields of cyclized uroducts." %
1.5-diene
A
diastereomer ratio L
O
A
other acetates (yields, %)
.
4 3 (23)
42
OAc
4 4 (16)
-p OAc
45
S
O
A
C
47 ( 6 ) 46 (23)
>75/25
54
67/33
18
AcO
48 498
tcis.33)
4 9 b (trans,67)
" Catalytic conditions, cf. Experimental Section. Pd(0Ac)z 1 equiv. Table 11. Cyclization of 1,3-Disubstituted 1,5-Hexadienes
Ph
26 - 2 9 53- 55 59- 64
34 Ph
30-33 65-73
a = trans b = cis A
Ph
O
A
''
c
35
compd no. 26, R = H 26, R = H 27, R = Me 28, R = CHzPh 29, R = Ac 53, R = (CHJZOH 54, R = (CH2)aOH 55, R = (CH2)dOH 59, R = (CHJ2CN 60, R = (CHz)&N 61, R = (CH2)dCN 62, R = CHpCOOH 63, R = (CHZ)&OOH 64, R = (CHZ),COOH
product no. 30 30 31 32 33 65 66 67 68 69 70 71 72 73
yields," % cyclic comud 34 35 43 38 42b 43b 41b 46 46 42 50 44b 46 40 43 46
8
15
Ib 7b lb 8 5 9 3 5b 8 8 7 7
15b 24b lgb 20 18 20 15 12b 15 17 16 20
trans/cis ratio 55/45 44/56= 54/46 57/43 52/48 60140 55/45 55/45 60140 58/42 59/41 70130 63/37 60140
* Catalytic conditions, cf. Experimental Section. Yields calculated on consumed starting material. CBenzoquinone,1 equiv, without MnOz.
bridgehead olefin 19 (Scheme I). The latter compound can also be obtained directly by the PdC12/CuC1,-catalyzed cyclization of diene 13.28a Palladium-catalyzed cyclization of the 1-substituted compound l-phenyl-1,Ei-hexadiene (20), which was obtained as the trans isomer by- Cope-rearrangement of 9,32 turned out to be highly stereo- and regioselective. This reaction yielded compound 21 with pure E configuration of the double bond as the main product (33%) along with the noncyclic acetate 22 (4%) (formed by allylic oxidation (32)Dewar, M. J. S.;Wade, L. E., Jr. J.Am. Chem. SOC.1977,99,4417.
of 2033) and two unidentified noncyclic acetates ( l l % , Table I). However, cyclization of the cis isomer 23, prepared via condensation of benzaldehyde and l-(Cpenteny1)diphenylphosphineoxide, proceeded with considerably lower stereoselectivity, affording a 79/21 mixture of the expected 2 isomer 24 and the E isomer 21, along with the noncyclic acetate 25. Methods for the preparation of cyclopentane rings with oxygen functionalitiesare of great interest for the synthesis of various natural products. Therefore, cyclizations of the 1,3-disbustituted l,&dienes 26-29 carrying oxygen functionalities in the 3-position were attempted (Table 11). These dienes were conveniently prepared from cinnamic aldehyde and allyl bromide in the presence of tin and aluminum.34 They cyclized smoothly when subjected to the reaction conditions to yield the acetoxycyclopentanes 30-33 (41-43%), all with pure 2 configuration of the double bonds. As expected, the products consisted of mixtures of the trans and cis isomers, in each case with a slight excess (ca. 55/45) of the former. All cyclizations of 3-0-substituted 1,5-dienes were accompanied by the formation of high quantities of the conjugated acetates 34 and 35 (1-8 and 15-24%, respectively, see Table 11). The noncyclic acetates were shorn to be formed via palladium-catalyzed since only starting material was recovered in blank experiments without the noble metal catalyst. (Z)-3-Hydroxy-l-phenyl-l,5-hexadiene (37) (prepared by LiBH4 reduction of cis-methyl cinnamateB in methanol% followed by oxidation3' to cis-cinnamic aldehyde and coupling with allyl magnesium bromide) afforded, in addition to the expected cyclic products 38a and 38b (22%) and some unidentified noncyclic products, the 2 isomers 30a,b (14%, Table I). Cyclization of the 2 isomer proceeded, however, with considerably higher stereoselectivity with respect to the substituents on the ring than cyclization of the E isomer, the ratios of 38a/b and 30a/b being 74/26 and 85/15, respectively. 1,5-Dienes with substituents in the 1-position carrying a-hydrogens did not afford exomethylenecyclopentanes, (33) For allylic oxidation reactions with a similar catalyst, cf.: Heumann, A.; hermark, B. Angew. Chem., Znt. Ed. Engl. 1984, 23, 453. Heumann,A.; hermark, B.;H-son, S.; Rein, T.0%. Synth., in pres. (34) Nonami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics 1983. 2. lgl.
(35)'Engler,T.; Falter,W. Tetrahedron Lett. 1986, 27, 4119. (36) Soai, K.; Oookawa,A. J . Org. Chem. 1986,51,4000. (37) Fatiadi, A. J. Synthesis 1976, 65.
4918 J. Org. Chem., Vol. 54, No. 20, 1989
but rather yielded the corresponding vinyl compounds. (39) gave the hyFor example, 4-hydroxy-l,5-heptadiene droxyacetate 40 (41%) as a mixture of all four possible diastereomers, along with the conjugated noncyclic diacetate 41 (lo%, Table I). The four diastereomers 40a-d could be separated by HPLC and characterized by 'H NMR spectroscopy, but the stereochemistry of the individual products could not be assigned. Attempted cyclization of the alcohol 42, containing one trisubstituted double bond, resulted in allylic oxidations*%affording the hydroxyacetates 43 (23%) and 44 (16%), the latter as a 40160 mixture of two diastereomers. Likewise, no cyclized products were obtained from 2-allylcyclohexene (45). Instead, allylic oxidation took place to afford on 80/20 ratio of 3-(l-acetoxy-2-propenyl)cyclohexene(46) and 3-acetoxy-6-(2-propenyl)cyclohexene(47) in 29% yield, together with some unidentified products. Some experiments were performed using modified oxidation systems, resulting in significant effects on product patterns. When a stoichiometric amount of p-benzoquinone and no MnOz was used for the reoxidation of Pd(0) in the cyclization of the alcohol 26 (Table 11),the trans and cis isomers (30a,b) were obtained (38%) in a reverse ratio (44156, compared to 55/45 for the reaction using a catalytic amount of p-benzoquinone). The use of a stoichiometric amount of palladium acetate and no reoxidant in the cyclization of the methyl ether 27 resulted in a 12150138 ratio of the acetoxyexomethylenecyclopentanes 31a and 31b and the allylic acetate 36 (Table I). Since the substituents in the latter compound assume a trans c o n f i g u r a t i ~ nthe , ~ ~formation of 36 is thought to occur via isomerization of the trans isomer 31a, implying a diastereomeric ratio of 50150 of the primary products. Since no higher diastereoselectivity was observed, the effects of further modifications were not investigated. In order to investigate whether steric crowding of the benzoquinone would affect the diastereoselectivity, pbenzoquinone supported on polystyrene-divinylbenzene was used as oxidant in the cyclization of 3-phenyl-1,5hexadiene (9). The polymeric reagent proved to be useful for the cyclization, but the cisltrans ratio of the product (loa/ lob) was similar to that obtained using monomeric benzoquinone (about 50150). We have previously observed that cyclization of the allylic acetate 48 yields acetoxycyclopentanes 49 with a transfcis ratio of 67/33.29 It does not seem plausible that the reason for this rather high preference for the trans isomer is a favored pseuodoequatorial substitution of the palladium-diene complex originating from the bulkiness of the substitutent, since no such preference was observed for 3-phenyl-1,5-hexadiene (9). Since square-planar palladium(I1) complexes have a tendency to become five coordinate,4O weak coordination of the acetate group to palladium may be considered as the reason favoring a pseudoequatorial palladium-diene complex. In order to investigate whether increased stereoselectivity may result from the presence of a functional group capable of coordination to palladium, a series of 3-0-substituted 1,5-hexadienes carrying alcohol, nitrile, and car(38)Heumann, A.; Reglier, M.; Waegell, B. Angew. Chem., Int. Ed. Engl. 1982,21,366;Angew. Chem. Suppl. 1982,922. (39)This result can be explained by the initial formation of a CB. 50/50 mixture of the expected trans and cis isomers 31a and 31b. i.e. a similar ratio to that observed under catalytic conditions, followed by rearrangement of the trans isomer to yield 36. Since the zero-valent palladium formed during the cyclization is not reoxidized under these conditions, it seems reasonable to assume that the rearrangement is catalyzed by Pd(0). (40)Wilkinson, G.; Stone, F. G. A.; Abel, E. W. Comprehensiue Organometallic Chemistry; Pergamon Press: Oxford, 1982;Vol. 6, p 233.
Antonsson et al. Scheme IIa OH
A
Ph
26
O-(CH2),-
OTH P
ph4.Lb
O-(CH?),-OH Ph4
J
53: n = 2 (81%) 54: n = 3 (82%) 55: n = 4 (65%)
50: n 2 (67%) 51: n=3 (34%) 52: n = 4 (91%) =t
IC
9/
O-(CH& -C N
0 - (C H2)n- OTS
Ph& A / + &Ph
59:n=2(90%) 60: n 3 (96%) 61:n=4(99%)
L
J2),-COOH Ph
56 : n = 2 ( 9 5 % ) 5 7 : n = 3(93%) 58:n=4(98%)
62: n = l (46X) 63: n = 2 ( 2 6 % ) 6 4 : n = 3(66%)
'(a) Cl-(CH,),-OTHP, KOH, DMSO, 40 "C; (b) p-TsOH, MeOH, room temperature; (c) pyridinium dichromate, DMF, (d) TsCl, pyridine, 0 OC; (e) NaCN, DMSO, room temperature.
boxylic acid groups at various distances from the diene center were prepared. For this purpose, the alcohol 26 was reacted with tetrahydropyranyl ethers of a,u-chloro alcohols containing 2, 3, and 4 carbon atoms (Scheme 11). After deprotection, the alcohols 53-55 were obtained. These alcohols were tosylated to give compounds 56-58, which were converted to the desired nitriles 59-61. The carboxylic acids 62-64 were finally obtained by oxidation of the alcohols 53-55. The results of the cyclizations of the above compounds are shown in Table 11. In the absence of coordinating ability of the substituents, transfcis ratios comparable to those observed upon cyclization of the dienes 26-29, i.e. approximately 50150, are expected. For several of these compounds somewhat higher ratios were observed, which may indicate a weak chelation effect in the cyclization. Structure Elucidation. The stereochemistry of the cyclized products was determined by NMR methods. A cis stereochemistry was assigned to compound 10a due to a 3.5% NOE effect of the ring proton adjacent to the phenyl group (C5-H) upon irradiation of the proton next to the acetoxy group (C3-H) and the lack of an NOE effect of the other isomer. Due to the characteristic coupling 3.5%NOE
Ph 10a (cis)
pattern for the proton next to the acetoxy group (a triplet of triplets for the trans isomer and a quintet for the cis isomer) in acetoxymethylenecyclopentaneswith substituents in 2-position, the stereochemistry of these compounds could be deduced from that of 10. The structures of the indan derivatives 15, 16, and 19 were determined by high resolution NMR spectroscopy (Table 111). In acetate 19, a tetrasubstituted olefinic group was indicated by the presence of two signals from sp2 carbons in the 13CNMR spectrum (6 135.3, C1, and 125.1, C9), and by the absence of signals from vinylic protons in the lH NMR spectrum. Furthermore, a resonance from a vinylic methyl group lacking 2J and 3J couplings was identified at 6 1.6. The steieochemistry (endo or exo) was determined from the coupling constants. Inspection of molecular models suggests that the dihedral angles between the hydrogen adjacent to the functional group (C7-H) and the neighbouring hydrogens at C6 and C8 are quite different in the two stereoisomers. According to the Karplus equation;l the proton resonance pattern should be different in compounds whose stereochemistry differ
J. Org. Chem., Vol. 54, No. 20,1989 4919
Palladium-Catalyzed Oxidative Cyclization
Table 111. 'HNMR Resonances of Indan Derivatives"
2.38
4.84 (8
+ 4 + 4)
2.69 (16 + 8)
2.23 (16)'
19
cab
2.72
1.91
3.99 (6 + 3 + 3)
2.81 (18+ 6)'
2.30 (18)'
2.55
2.28
5.05
2.44 (17.5 + 8)c
2.82 (17.5+ 8)
2.86 (17 + 8)
2.16 (17 + 8)'
2.41 (19)
2.69 (19 + 6)
n
15a
am
(8
+ 8 + 6)
H
16a
ab
2.0 - 2.11
3.85 (8
+ 8 + 4)
15b
2.0 - 2.18
5.21 (6 + 3)
16b
400 MHz, we thank H. Kolshorn, University of Mainz, for very valuable help with the NMR spectra. *In the corresponding acetates 14 and 18 the H7 signals (6 = 4.82 and 4.72 ppm, respectively) are partially or totally hidden by the patterns of the vinylic protons. 'Additionally there is a number of small (2-2.5 Hz)couplings. dPrepared from 15b according to ref 31. a
at C7. In compound 19,the dihedral angles between C7-H and C6-H, and between C7-H and C8-HeX,,are both estimated to approximately 130°, whereas the dihedral angle between C7-H and C8-H,,d0 is approximately loo. The signal observed (6 4.84, dt, J1= 8, J2 = J3 = 4 Hz, Table 111) corresponds nicely to this arrangement. In the case of cyclopentanes, caution is required when the relative stereochemistry of two (or more) groups is to be determined by the Karplus equation.42 In our molecule, however, annulation of the six-membered ring decreases the conformational mobility of the five-membered ring, rendering the above analysis plausible. The stereochemistry of compound 14 (and the derived alcohol 15a)was verified by isomerization of 14 to 19,a process which does not affect the stereochemistry at C7 (Scheme I). Additional support for our stereochemical assignments is provided by the 'H NMR spectrum of alcohol 15a, as well as that of the endo-acetate 16a. Although the coupling constants are more difficult to predict in these more mobile systems, the differences in chemical shifts between the C&Hdoprotons of 14 and 16a (6 2.83 and 2.44, respectively) and of the C7-HeX0protons of the two epimers (6 2.35 and 2.82, respectively, Table 111)are consistent with our interpretation. The same arguments can be used to verify stereochemical assignments for compounds 15b, 16b,and 18. The stereochemical assignments of acetoxymethylenecyclopentanes 30-33 were made by results from NOE ex(41)Giinther, H. NMR Spektroskopie, 2nd ed.; G. Thieme: 1983;p 105.
(42)Stereochemistry, Vol I : Determination of Configurations by Spectrometric Methods; Kagan, H. D., Ed.; G. Thieme: Leipzig, 1977; p
89.
periments. The stereochemistry of the exocyclic double bond was deduced from irradiation of the olefinic proton next to the phenyl group. Compounds 30a and 30b gave a total enhancement of 44% and 18%, respectively, of the methylene protons (C5-H2),indicating 2 configuration of the oIefins. Irradiation of the proton adjacent to the 44%NOE H
AcO
18%NOE H
f l
OH 30a(trans)
\
OH
3 Obtcis 1
acetoxy group (C4-H) in compound 30a resulted in a 9% enhancement of the resonance for the hydroxyl proton. This effect was absent in compound 30b,and, therefore, 30a was assigned a trans stereochemistry. The stereochemistry of compounds 31-33 as well as of 65-73 was assigned by comparison of the 'H NMR and 13C NMR spectra of these compounds with those of 30a and 30b. Mechanistic Aspects. 1,5-Dienesare known to readily complex to palladium(II), and such complexes have been the subject of extensive e ~ p e r i m e n t a as l~~ well as theoretical" studies. Although they are thermodynamically quite stable, they react with nucleophilesfi to form new (43)Holloway, C.E.; Hulley, G.; Johnson, B. F. G.; Lewis,J. J. Chem. SOC.A 1969,53. Zakharava, I. A.; Leites, L. A.; Aleksanyan, V. T. J. Organomet. Chem. 1974,72, 283. (44)Albright, T. A.;Hohann, R.; Thibault, J. C.; Thorn,D. L. J. Am. Chem. Soc. 1979,101,3802.Ziegler, T.; Rank, A. Znorg. Chem. 1979,18, 1558.
(45)Blckvall, J. E. In Reaction of Coordinated Ligands; Praterman, P. S., Ed.; Plenum Press: New York, 1986.
4920
J. Org. Chem., Vol. 54, No. 20, 1989
Antonsson et al.
Scheme I11
Scheme IV .OAc tram attack O f acetate
A
B
trans addition Of
addition of acetate
acetate
t r a n s - 1 -phenyl-1.5- hexadiene ( 2 0 )
1
J?
pJ,-$f~ - rJ' H i Ph
addition O f acetate \
OAc
insartion
OAc
p
rotation
AcO
-Pd-
AcO
I
h B-elimination_
H2
OAc
A
R
trans- 1,3 isomer
cis-1.3 isomer
carbon-heteroatom bonds. With conformationally nonrestricted olefins, these complexes adopt a pseudosquare-planar coordination with two double bonds aligned perpendicular to the coordination plane. It seems highly likely that the first step in the palladium-catalyzed cyclization of 1,bdienes is the formation of a di-?r-palladium-diene complex and also that the different selectivities observed during the reactions are closely related to the structure of this (these) complex(es). The unreactivity of diene 45 (with respect to cyclization) supports this hypothesis since, for steric reasons, this olefin is unlikely to form such a palladium-diene complex. However, similar dienyl cyclohexene derivatives, with an oxygen-substituted double bond in the ring, have been cyclized with stoichiometric amounts of palladium(II).24 Furthermore, the allylic oxidation products from 45, as well as those from dienes such as 4-~inylcyclohexene,~ are formed via Pd catalysis, and consequently, via a coordination step. The second important selectivity-controlliig step is the acetate attack at one of the coordinated double bonds. Markovnikov type addition occurs, rendering the reaction completely chemoselective. At the same time, the diastereochemistry of the cyclization of 3- and 3,4-substituted dienes is determined. The formation of two diastereomers may be due either to nucleophilic attack on two isomeric palladium complexes A and B (Scheme 111), or to competing cis and trans attack of the nucleophile (relative to palladium, Scheme 111). It has been demonstrated that, in chloride-free acetic medium, the acetate attack on olefins coordinated to palladium occurs in a stereospecific trans fashion.& In addition, considering the high diastereoselectivity observed upon cyclization of cis-1,2-divinylcyclohexane (13), competing cis and trans attack of acetate seems highly improbable. Instead, inspection of molecular models suggests that one isomer of the palladium complex of 13, with the cyclohexane ring either in a boat conformation (C, with efficient coordination of both
D
double bonds to palladium), or in a chair form (D, with a more stable conformation of the ligand) should be considerably more stable than other possible isomers, which suffer from severe hydrogen-hydrogen interactions or have unfavorable diaxial substitution patterns. Trans attack (46) Andell, 0. S.; Bickvall, J. E. J.Organomet. Chem. 1983,244,401.
21
of acetate on either of these preferred isomers (C or D) would, indeed, lead to the observed stereoi~omer.~~ For the noncyclic 3-substituted dienes, the two different isomers A and B are expected to be about equally stable, leading to the observed mixtures of diastereomers (their ratios ranging from 50150 to 57/43 for products obtained by acetate attack at C5). The addition of a phenyl substituent at C1 in a trans configuration does not alter this picture. For 1-cis-substituted l,bdienes, however, complexes with pseudoequatorial substituents should be more stable, and, therefore, higher amounts of cyclic trans compounds are expected. This is in accordance with our findings. Our experimental results are, thus, nicely explained by initial formation of, depending on the structure of the diene, either one palladium-diene complex and the observation of high diastereoselectivity, or two isomeric such complexes and less selective reaction. The cyclization step can be explained by the insertion of the second olefii of the a-?r-palladium complex (formed after the addition of the nucleophile to the di-?r-olefin complex) into the Pd-carbon u bond. The elimination of palladium hydride liberates the cyclic organic product (Scheme IV). Both of these processes are known to be cis-stereospecific.@ This feature is well demonstrated by the stereospecific formation of E exocyclic olefins (with respect to the acetate) from trans-1-phenyl-substituted 1,5dienes 20,26-29 (Table I). The reaction of cis-1-phenyl 1,5-dienes 23 and 37, however, seems to be much less straightforward in both cases, the major products are the expected Z stereoisomers, but, in addition, considerable amounts of the unexpected E isomers are formed. This observation may be explained by an isomerization process. An isomerized starting olefin should also give, as a side product, some isomerized allylic acetate. However, we could not detect any acetate 22 from 23! On the other hand, we have never observed any isomerization of the exocyclic double bond with the oxidizing system used for the cyclization reactions. Thus, at the present time, it seems difficult to rationalize the isomerization process. Conclusions We have shown that the catalytic system palladium acetate/ benzoquinone/manganese dioxide promotes cyclization of a great number of acyclic and cyclic 1,5-dienes. (47) A mechanistic study on this particular problem is in progress. (48)Collman,J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications of Orgumtransition Metal Chemistry; University Science Books: California, 1987.
J . Org. Chem., Vol. 54, No. 20, 1989 4921
Palladium-Catalyzed Oxidative Cyclization
In acetic acid" a Wacker type catalytic reaction takes place to yield cyclopentanes with acetate a n d exomethylene groups in a 1,3 configurational relationship. Substituents in the 1,3-and/or Cpositions of the 1,5-dieneare tolerated, but n o t in the 2- a n d 5-positions. As a consequence, this oxidation constitutes a general, synthetically usefulm method for t h e preparation of 1,3- or 1,3,5-substituted five-membered carbocycles. T h e preparation of the starting olefins is performed by general routes, e.g. the allylic coupling reaction. One drawback to these reactions is the undesirable allylic rearrangement, affording mixtures of isomers. T h i s has been overcome b y several highly selective, primarily metal-catalyzed reaction^.^^ Furthermore, i t has been shown that the cyclization reaction is compatible with the presence of different functional groups: alcohols, acetates (including allylic acetates), ethers, nitriles, and carboxylic acids. I n general, no isomerized products have been found. T h e diastereoselectivities depend strongly upon the structure of the starting olefin; fairly good t o very good diastereoselectivity ratios have been observed.
Experimental Section General Methods. 'H NMR and 13C NMR spectra were recorded on a Bruker WP 200 FT spectrometer (200 and 50.3 MHz) or on a Bruker AM 400 FT spectrometer (400 and 100.6 MHz, respectively). 'H NMR spectra were recorded in CDC13 with Me4Si as internal standard. 13C NMR were recorded in CDC13 (CDC136 77.0 as internal standard unless otherwise stated) or in CD3C0 (CD3C0 6 29.8 as internal standard). DEPT (distortionless enhancement by polarization transfer) spectra were determined to assign carbon multiplicities (s, C; d, CH; t, CH2; q, CH3). Nuclear Overhauser Enhancement (NOE) experimenta were performed in degassed CDC13. Analytical GLC was performed on a Pye Unicam Serie 207 instrument using a 30 m X 0.237 mm DBWAX column or a 25 m X 0.2 mm Carbowax 20 M column, a Varian Model 3700 instrument using a 25 m X 0.2 mm cross-linked methylsilicone capillary column or on a Pye GCD chromatograph using a 1.2 m X 2 mm glass column of 5% SE-30 on Chromosorb W. Infrared spectra were run on a Perkin-Elmer 257 spectrometer. High-pressureliquid chromatography (HPLC) was performed on a Waters M-45 instrument with a microporasil column (silica, 10 wm packing, 0.4 cm X 30 cm). Melting points were measured on a Biichi 510 apparatus and are uncorrected. Mass spectra were run on a LKB 9000 and on a Finnigan 4021 GLC-MS instrument a t 70 eV. For slow additions a Sage Instruments Model 355 syringe pump was used. Flash chromatography was done according to the method described by Still, Kahn, and MitraS2using silica gel 60 (230-400 mesh) obtained from Merck. By "in vacuona rotary evaporator operating at water aspirator pressure is meant. Microanalyses were performed by Analytical Laboratories, Engelskirchen, Germany, and by the "Service de Microanalyse de la Facult2 de St. JgrBme", Marseille, France. Materials. Palladium(I1) acetate obtained from Engelhardt, 3-methy1-1,ti-hexadienefrom Aldrich, 1,5-hexadiene, cis- and trans-1,2-divinylcyclohexanefrom Fluka, and p-benzoquinone and Mn02 from Merck were used as received. n-BuLi (Aldrich) was titrated with benzyl alcohol using 1,lO-phenanthroline as indicator. Polymer-supported p-benzoquinone was prepared by a literature procedure from chloromethylated polystyrene-2 % divinylben~ene.~~ 3-Methylbutenal was a generous gift from (49) Other carboxylic acids can be added to 1,bdienes under similar conditions; thus chiral acids lead to significant optical induction, Heumann, A.; Moberg, C. J. Chem. Soc., Chem. Commun. 1988, 1516. (50) This cyclization constitutes the key step in a formal synthesis of (A)-Sativene: Antonsson, T.; Malmberg, C.; Moberg, C. Tetrahedron Lett. 1988, 29, 5973. (51) Hosomi, A.; Imai, T.; Endo, M.; Sakuri, H. J. Organomet. Chem. 1985,285,95. Calo, V.; Lobez, L.; Pesce, G. J. Chem. SOC.,Chem. Commun. 1985,1357. Rossi, R.; Carpita, A. Tetrahedron Lett. 1986,27,2529. Guao, B.-S.; Doubleday, W.; Cohen, T. J. Am. Chem. SOC.1987,109,4710. (52) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
BASF. Hexane, petroleum ether (bp 3&50 "C), pentane, and ethyl acetate were distilled before use. Dry EhO and THF were obtained by distillation from benzophenone ketyl. Dimethyl sulfoxide (DMSO) was dried with activated molecular sieves (4A). Acetic acid (puriss) was used as received. Cyclization of 1,5-Hexadiene (1). 1,5-Hexadiene (164 mg, 2 mmol) was added to a well-stirred mixture of Pd(OAcI2(22 mg, 0.1 mmol), Mn02 (174 mg, 2 mmol), and benzoquinone (54 mg, 0.5 mmol) in 10 mL of acetic acid. After the mixture was stirred a t ambient temperature for 42 h, 5 mL of brine was added and the reaction mixture was filtered. The filter cake was washed with 20 mL of pentaneIEh0 (7/3), and the mother liquor was extracted with 5 X 20 mL pentaneIEh0 (713). The combined organic phase was then washed with 5 mL of HzO and 3 X 5 mL of saturated aqueous Na2C03and dried (MgSO,). Removal of the solvent a t atmospheric pressure gave 245 mg of a dark oil. Purification of the crude product by flash chromatography (9/1 pentane/Et20) gave 202 mg (72%) of a 65/25/10 mixture of 2, 3, and 4. Spectroscopicdata for compound 2 were in agreement with earlier data.26b293: 'H NMR (200 MHz) 6 5.35 (tt, J = 7 Hz and 2.7 Hz, 1 H, methine proton), 5.30 (br s, 1 H, olefinic), 2.83-2.58 (m, 2 H, allylic), 2.43-2.12 (m, 2 H, allylic), 2.03 (s, 3 H, OAc), 1.74 (br s, 3 H, Me). Cyclization of 3-Methyl-lP-hexadiene(5). The cyclization of 5 was performed on a 1-mmol scale following the procedure described for the cyclization of compound 1, except that merely 0.75 mmol of Mn02 was used. After the mixture was stirred at ambient temperature for 27 h, brine (10 mL) was added, the aqueous phase was extracted with petroleum etherfEh0 (3 X 20 mL 812, 10 mL 7/3), and the organic phase was washed with saturated NaHC03 (4 X 10 mL) and dried (MgSO,). The solvent was evaporated in vacuo using a bulb-to-bulb apparatus. Flash chromatography (using a stepwise gradient of petroleum ether/EhO, 8/2,7/3,6/4,5/5,4/6,50 mL of each) yielded a mixture of compounds 6-8 (49%) along with trace amounts of some unidentified acetates. Selected peaks from the 'H NMR spectrum of the isomeric mixture: 5.18 (tt,J = 5.5 and 2 Hz, 1H, CH(0Ac) in 6b), 5.09 (quintet, J = 6 Hz, 1H, CH(0Ac) in 6a), 4.84-4.87 and 4.89-4.93 (m, CH2= in 6a and 6b), 2.26-2.34 (m, 1H, allylic in 6a), 2.01-2.09 (3 s, OAc), 1.63 (t, J = 1 Hz, 3 H, CH3 in 7), 1.45-1.53 (ddd, J = 13.5, 11 and 5 Hz, 1 H, CH2CHCH3in 6b), 1.39-1.44 (m, 1 H, CH2CHCH3in 6a), 1.15 (d, J = 6.8 Hz, 3 H, CH3in sa), 1.11(d, J = 6.7 Hz, 3 H, CH3in 6b), 1.03 (d, J = 7.1 Hz, 3 H, CH3 in 8a or 8b), 0.98 (d, J = 6.9 Hz, 3 H, CH3 in 8a or 8b). 3-Phenyl-1,5-hexadiene(9). n-BuLi (1.45 M in hexane, 31 mL, 45 mmol) was added during 10 min to a stirred slurry of triphenylmethylphosphonium bromide (16.1 g, 45 mmol) in 70 mL of anhydrous E g o under a nitrogen atmosphere. After the mixture was stirred for 2 h at ambient temperature, 2-phenyl4-pentenal (4.8 g, 30 mmol)" dissolved in 17 mL of anhydrous EhO was added during 80 min, and the mixture was stirred for an additional 22 h. E t 0 was added to the reaction mixture, and the precipitate formed was removed by filtration. The organic phase was washed with water until the aqueous phase became neutral and dried (MgSO,). The solvent was removed in vacuo to afford 3.86 g of a slurry. Following flash chromatography (silica gel, EhO/pentane, 1/9) 1.2 g (7.6 mmol, 25%) of 9% was obtained. Cyclization of Compound 9. The procedure described for compound 5 was used for the cyclization of 9 (1 mmol). After the mixture was stirred at ambient temperature for 29 h, 10 mL of brine was added and the aqueous phase was extracted with 3 X 20 mL and 10 mL of pentane/Et20 (4/1). The combined organic phase was washed with water (5 mL) and saturated aqueous Na2CO3(2 X 5 mL) and dried (MgSO,). Removal of the solvent in vacuo afforded 196 mg of a brown oil. The crude product was flash chromatographed (EhO/hexane, 1/4) to give a mixture (130 mg, 60%) of loa, lob, 11, and 12 in a ratio of 45/42/10/3, as determined by capillary GLC (carbowax 20 M). Compound 10b was obtained in a pure form from the mixture by crystallization with hexane at -20 OC. The other isomers were separated by HPLC (hexane/EtOAc 9812) for structural deter~~~
(53) Kun, K.A. J. Pol. Science: Part A 1965, 3, 1833. (54) Elkik, E. BulZ. SOC.Chim. 1969, 903. (55) Dewar, M. I. S.; Wade, L. E., Jr. J.Am. Chem. SOC.1977,99,4417.
4922 J . Org. Chem., Vol. 54, No. 20, 1989 mination. loa: 'H NMR (200 MHz) 6 7.15-7.4 (m, 5 H, Ph), 5.2 (quintet, J = 7 Hz, 1 H, CHOAc), 4.98-5.05 (m, 1 H, CH2=C), 4.53-4.60 (m, 1 H, CH,=C), 3.65 (br t, J = 10 Hz, 1 H, CH(Ph)), 2.83-3.02 (m, J , , = 17 Hz, 1 H, =CCH2), 2.45-2.67 (m, 2 H, CHZCH(OAc)C!Z2),2.04 (s, 3 H, OAc), 1.86-2.05 (ddd, J = 13, 10, and 7 Hz, 1 H, CH,CHPh); 13CNMR (100.6 MHz) 6 170.86, 152.04, 143.47, 128.37, 128.32, 126.36, 109.30, 73.62, 48.35,41.01, 39.68,21.18. Anal. Calcd for CI4H16O2: C, 77.73; H, 7.46. Found: C, 77.48; H, 7.49. lob: 'H NMR (200 MHz) 6 7.15-7.4 (m, 5 H, Ph), 5.33 (br t, J = 5 Hz, 1 H, CHOAc), 4.98-5.06 (m, 1 H, CH2=C),4.58-4.65 (m, 1 H, CH2=C),3.78-3.94 (m, 1 H, CHPh), 2.81-2.98 (m, 1H,=CCH2),2.55-2.7 (m, 1H,=CCH2),2.24-2.39 (m, 1 H, CH,CHPh), 2.07 (s, 3 H, OAc), 1.95-2.13 (m, 1 H, CH,CHPh); '3c NMR (100.6 MHz) 6 170.81,152.93,143.35,128.45, 128.24, 126.41, 109.13,74.59,48.40,41.85,40.05,21.37.Anal. Calcd for C14H1602: C, 77.73; H, 7.46. Found: C, 77.65; H, 7.37. 11: 'H NMR (200 MHz) 6 7.15-7.45 (m, 5 H, Ph), 6.6-6.75 (m, 2 H, C=CHCH(OAc)), 3.5-3.65 (m, 1 H, CH(Ph)),2.8-3.0 (m, 1 H, CH,), 2.07 (9, 3 H, OAc), 1.75-1.9 (m, 1H, CH,), 1.55 (br s, 3 H, Me). 12: 'H NMR (200 MHz) 6 7.15-7.4 (m, 5 H, Ph), 5.15 (q, J = 7 Hz, 1 H, CHOAc), 4.92-5.06 (m, 2 H, CH,=C), 3.32 (q, J = 7 H, 1 H, CHPh), 2.78-3.04 (m, 2 H, CH2(CH2=C)CH,), 2.45-2.67 (m, 1 H, CH2CHPh),2.27-2.45 (m, 1 H, CH,CHOAc), 2.01 (s, 3 H, OAc). Cyclization of cis -1,2-Divinylcyclohexane(13). To a well-stirred mixture of P ~ ( O A C(112 ) ~ mg, 0.5 mmol), Mn02 (870 mg, 10 mmol), and benzoquinone (216 mg, 2 mmol) in 50 mL of acetic acid was added 13 (1.36 g, 10 mmol), and the mixture was stirred at ambient temperature for 42 h; 10 mL water was added, and the aqueous phase was extracted with petroleum ether. The organic phase was washed with 2 M NaOH and water and dried (MgSO,). Removal of the solvent in vacuo and flash chromatography (petroleum ether/EhO, 97/3) afforded 1.35 g (7 mmol, 70%) of 14: 'H NMR (400MHz) 6 4.90 (br, w1 = 6 Hz,1 H, = 9.5 Hz, 2 H, CH2=C$, 2.83 (m, part CH(OAc)),4.82 (br, of AB, J = 18, 7.5, 2.5, and 2.5 Hz, 1H, CH2CH(OAc)),2.67 (br, w1 = 15 Hz, 1 H), 2.35 (d, part of AB, J = 18 Hz, 1 H, Ch2CH(OAc)), 1.98 (9, 3 H, OAc), 1.93-2.08 (m, 1 H), 1.75 (br, q2 = 21 Hz,1H), 1.57-1.7 (m, 3 H), 1.27-1.36 (m, 2 H), 1.13-1.27 (m, 1H), 0.85-0.96 (m, 1H); 13CNMR (100.6 MHz) 6 170.7, 150.5, 105.8, 76.7,44.8,41.2,37.5, 25.5,25.2,24.1, 21.6, 21.2. Anal. Calcd for C12Hls02: C, 74.19; H, 9.34. Found: C, 74.18; H, 9.30. Cyclization of trans-1,2-Divinylcyclohexane(17). Compound 17 (272 mg, 2 mmol) was cyclized under the same conditions as 13 (72 h reaction time). Workup according to the procedure described for 13 gave 250 mg (1.29 mmol, 64%) of a mixture of 18,19 (87/13, 54%), and two other unidentified monoacetates in a ratio of 64/36 (10%). 18: 'H NMR (400 MHz) 6 4.67-4.75 (m, 3 H), 2.93 (m, 1H), 2.01 (s,3 H), 1.88-2.14 (m, 3 H), 1.63-1.80 (m, 3 H), 1.00-1.37 (m, 5 H); 13CNMR (100.6 MHz) 6 171.2, 150.7, 103.4,76.7,50.3,46.7,37.5, 29.5, 28.4, 25.6, 25.4,20.99. Anal. Calcd for ClzH1802: C, 74.19; H, 9.34. Found: C, 74.33; H, 9.32. Hydrolysis of Acetate 14. To a solution of 14 (1.098 g, 5.68 mmol) in 20 mL of MeOH was added 3.4 mL of 2 M NaOH (6.8 mmol), and the mixture was heated to reflux for 5 min. MeOH was removed in vacuo, 10 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (30 mL, 8/2, 30 mL, l/l). The organic phase was dried (MgSO,), and the solvent was removed in vacuo to give 829 mg of a yellow oil. Bulb-to-bulb distillation (170 OC, ca. 0.5 Torr) afforded 785 mg (5.16 mmol, 91%) of 15a as a colorless oil. 15a:R, = 0.28 (petroleum ether/Et20, 7/3); 'H NMR (400 MHz) 6 4.92 (m, 1 H, CH2=C), 4.84 (m, 1 H, C H 4 ) , 3.99 (dt, J = 6.2 and 3.0 Hz, 1H, CHOH), 2.81 (dd, J = 18 and 6 Hz, 1 H), 2.72 (m, 1 H), 2.3 (br d, J = 18 Hz, 1 H), 2.04-2.14 (m, 1 H), 1.91 (m, 1 H), 1.68-1.78 (m, 1 H), 1.46-1.63 (m, 3 H), 1.31-1.39 (m, 2 H), 1.2-1.32 (m, 1H), 0.96-1.06 (m, 1 H); 13CNMR (100.6 MHz) 6 151.37 (s), 105.62 (t),74.24 (d), 47.63 (d), 40.84 (d), 40.36 (d), 26.11 (t),25.44 (t),23.99 (t),22.07 (t). Cyclization of trans-l-Phenyl-1,5-hexadiene (20). The diene 20 was prepared by Cope rearrangement of 9 (230 "C, 3 h; the 'H NMR spectrum of 20 was in accordance with literature data55)and cyclized (1mmol scale) according to the procedure described for compound 9. After 43 h at ambient temperature 5 mL of brine was added, and the solution was extracted with petroleum ether/Et20 (3 X 20 mL, 8/2,10 mL, 7/3). The corn-
Antonsson et al. bined organic phase was washed with saturated aqueous NaHC03 (3 x 5 mL) and dried (MgSO,), and the solvent was removed in vacuo to yield 143 mg (66%) of a crude mixture, which was purified by flash chromatography with petroleum ether/EhO (8/2) to give a mixture of 21 (33%), 22 (40%), and two unidentified acetates (11%).The cyclic product 21 was separated from 22 by HPLC (hexane/EtOAc, 95/5). 21: 'H NMR (200 MHz) 6 7.06-7.31 (m, 5 H), 6.38 (quintet, J = 4 Hz, 1 H, =CH), 5.18-5.28 (m, 1 H, CHOAc), 2.5-3.0 (m, 4 H), 1.9-2.1 (m, 2 H), 2.03 (s, 3 H). 22: 'H NMR (200 MHz) 6 7.08-7.45 (m, 5 H), 6.42 (A part of ABX2, JAB = 16 and J U = 0 Hz, 1 H, PhCH=), 6.21 (B part of ABXZ, JAB = 16 and JBX = 6.5 Hz, 1 H, PhCHECH), 5.87 (A part of ABX2, JAB= 15, J f i = 6 Hz, 1H, CH=CHCH,OAc), 5.68 (B part of ABX2,JAB= 15, JBx= 6 Hz, 1 H, CHCH20Ac),4.52 (dd, J = 6.1 and 0.9 Hz, 2 H, CH20Ac),2.98 (br t, J = 6 Hz, 2 H), 2.07 (s, 3 H). cis - 1-Phenyl-1,5-hexadiene(23). Diphenyl-l-(4-pentenyl)phosphine oxide was treated with 1 equiv of LDA, and the resulting anion reacted with benzaldehyde to yield erythro-2-(diphenylphosphinoyl)-l-phenyl-5-hexen-l-ol, which in turn was treated with 1 equiv of NaH in dry DMSOMto afford 23 and 20 in a ratio of 85/15. Chromatography on a silica gel column impregnated with AgN03 (a stepwise gradient of petroleum ether/Et20, 99.5/0.5, 99/1, 98.5/1.5, etc. was used) yielded 23 (99% pure by GLC). The phosphine oxide: 'H NMR (200 Hz) 6 7.3-7.8 (m, 10 H), 5.60-5.85 (m, 1 H), 4.90-6.05 (m, 2 H), 2.05-2.35 (m, 4 H), 1.58-1.85 (m, 2 H); IR 1176 cm-' (P=O). The betaine: 'H NMR (200 MHz) 6 7.4-8.1 (m, 10 H), 7.1-7.4 (m, 5 H), 5.26 (br d, J p H = 9.5 Hz, 1H, CHOH), 5.10 (ddt, J = 17, 10, and 6.5 Hz, 1H), 4.80 (s, 1 H), 4.63-4.78 (m, 1 H), 4.43-4.59 (m, 1 H), 2.50 (br q, J p H = J" = 5.5 Hz, 1 H), 1.78-2.13 (m, 1 H), 1.40-1.78 (m, 1 H), 1.31 (br q, J = 7 Hz, 2 H). 23: 'H NMR (200 MHz) 6 7.1-7.5 (m, 5 H), 6.42 (br d, J = 11.5 Hz,1H, P h C H X H ) , 5.87 (ddt, J = 17, 10.5, and 6.5 Hz, 1 H, CH=CH2), 5.69 (dt, J = 11.5 and 7 Hz, 1H, PhCH=CH), 4.90-5.12 (m, 2 H), 2.44-2.55 (m, 2 H), 2.05-2.55 (m, 2 H). Cyclization of 23. The cyclization of 23 was performed on a 0.2-mmol scale following the procedure described for the cyclization of compound 1. The same workup procedure as that described for 5 afforded 39 mg of an oil. Flash chromatography (a stepwise gradient of petroleum ether/EtO, 99/1,98/2, 97/3, 96/4,95/5 was used) gave 9 mg (21%) of a mixture of cyclic (21 and 24) noncyclic (25)products, by capillary GLC in a ratio of 79/21. The ratio 24/21 was 79/21 by NMR. 24: 'H NMR (400 MHz, in mixture with 21 and 25) 6 7.25-7.40 (m, 5 H), 6.41 (quintet, 1 H, =CH), 5.28-5.33 (m, 1 H, CHOAc), 2.5-3.0 (m, 4 H), 1.8-2.0 (m, 2 H), 2.02 (s, 3 H); 13CNMR (100.6 MHz, Me4Si as internal standard) 6 170.90,142.18,138.11,128.29, 127.96,126.09, 122.71, 76.52, 37.72, 32.69, 31.19, 21.19. 25: 'H NMR (400 MHz, in mixture with 21 and 24) 6 7.15-7.40 (m, 5 H), 6.53 (br d, J = 11.5 Hz, 1 H, PhCH=), 5.8-5.9 (m, 1 H), 5.69 (dt, J = 11.5 and 7 Hz, 1H, PhCH=CH), 5.65-5.71 (m, 1 H), 4.55 (dq, J = 6.5 and 1 Hz, 2 H, CH,OAc), 3.08 (t of quintets, J = 7 and 1.5 Hz, 2 H), 2.06 (s, 3 H). Cyclization of trans-3-Hydroxy-l-phenyl-1,5-hexadiene (26).% This reaction was run on a 5-mmol scale using the procedure described for 9. After the mixture was stirred at ambient temperature for 45 h, 25 mL of brine was added and the aqueous phase was extracted with petroleum ether/EhO (2 X 40 mL, 7/3, 25 mL, l/l). The organic phase was washed with water (10 mL) and saturated aqueous Na2C03(15 and 10 mL). The combined aqueous phase was extracted with petroleum ether/EtzO (25 mL l/l),and the organic phase was washed with saturated aqueous Na2C03and dried (MgS04). The solvent was removed in vacuo to yield 1.023 g of an oil. Flash chromatography (a stepwise gradient of petroleum ether/Et20, 3/2, 1/1, and 2/3 was used) gave 34 (86 mg, 0.397 mmol), 35 (202 mg, 0.738 mmol), and a mixture of 30a and 30b (500 mg, 2.15 mmol, 43%) in a ratio of 55/45. The two diastereomers 30a,b were separated on HPLC (hexane/EtOAc, 9/1) for structural determination. 34: R, = 0.56 (petroleum ether/Et20, 2/3); MS m / e 216 (M+);'H NMR (200 MHz) 6 7.1-7.45 (m, 5 H, Ph), 6.72 (dd, J = 15 and 10 Hz, 1 H, (56) Buss, A. D.; Cruse, W. B.; Kennard, 0.; Warren, S. J. Chem. SOC. Perkin Trans. I 1984, 243.
Palladium-Catalyzed Oxidative Cyclization PhCH=CH) 6.55 (d, J = 15 Hz, 1 H, PhCH=CH), 6.40 (dd, J = 15 and 10 Hz, 1 H, PhCH=CHCH), 5.79 (dd, J = 15 and 6.5 Hz, 1 H, =CHCHOAc), 5.44 (apparent quintet, 1 H, CHOAc), 2.06 ( ~ ,H, 3 OAC),1.37 (d, J = 6.5 Hz, 3 H, CH3); 13CNMR (100.6 MHz) 6 170.30, 137.03, 133.52, 132.72, 131.88, 128.60, 127.92, 127.69, 126.41, 70.69, 21.36, 20.24. 35: Rf = 0.4 (petroleum ether/EhO, 2/3); MS m / e 274 (M'); 'H N M R (200 MHz) 6 7.15-7.45 (m, 5 H, Ph), 6.78 (dd, J = 15 and 10 Hz, 1H, PhCH=CH), 6.60 (d, J = 15 Hz, 1 H, PhCH=CH), 6.50 (dd, J = 15 and 10 Hz, 1 H, PhCH=CHCH), 5.71 (dd, J = 15 and 7 Hz, 1 H, = CHCHOAc), 5.58 (dt, J = 4 and 7 Hz, 1H, CHOAc), 4.27 (A part of ABX, JAB= 12, JAY = 4 Hz, 1 H, CH20Ac),4.14 (B part of ABX, JAB = 12, and JBX = 7 Hz,1H, CH~OAC), 2.10 ( ~ , H, 3 OAC), 2.07 (s,3 H, OAc); 13C NMR (100.6 MHz) 6 170.65,170.07,136.72, 134.70, 134.55, 128.63, 127.94, 127.38, 126.58, 126.52, 71.82,64.87, 21.11,20.77. 30a: Rf= 0.22 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.2-7.5 (m, 5 H, Ph), 6.50 (br s, w112 = 5 Hz, 1 H, C=CHPh), 5.36 (apparent quintet, 1H, CHOAc), 5.02 (br s, w112 = 12 Hz, 1 H, CHOH), 3.11 (br dd, J = 17 and 6.5 Hz, 1 H, =CCHz),2.53 (br d d , J = 17 and4.5 Hz,1H,=CCH2),2.24 and 2.14 (AB part of ABMX, JAB= 13.7, JAM= 4, Jm = 5.8, JBM= 5.5, and JBX = 5.5 Hz, 2 H, CH,CH(OH)), 2.03 (s, 3 H, OAC),1.74 (br s, 1 H, OH); 13CNMR (100.6 MHz) 6 170.85, 142.96, 136.57, 128.66, 128.29, 127.22, 127.01, 73.13, 70.18, 42.53, 39.54, 21.20; IR (film) 3600-3200,3060,3020,2970,1730,1600,1500,1250,1045, 750, 700 cm-'. Anal. Calcd for C14H1603: C, 72.39; H, 6.94; 0, 20.67. Found: C, 72.13; H, 6.85; 0, 20.54. 30b: Rf = 0.26 (petroleum ether/Et20, 2/3); 'H NMR (200 MHz) 6 7.55 (d, J = 7 Hz, 2 H, Ph), 7.2-7.4 (m, 3 H, Ph), 6.54 (br s, w1 = 6 Hz, 1 H, C=CHPh), 5.33 (br quintet, J = 4 Hz, 1 H, CdOAc), 4.80 (br s, w1 = 17 Hz, 1 H, CHOH), 2.84 (br s, wl12 = 8 Hz, 2 H, C=C!CHz), 2.1-2.27 (m, 3 H, CH(OH)CH2),2.06 (s, 3 H, OAc); 13CNMR (100.6 MHz) 6 170.34,143.15,136.74,128.53(2C),128.05, 127.21, 74.88, 70.96,42.41,40.29, 21.39; IR (film)3600-3200,2970, 1730, 1600, 1500, 1250, 1040, 760, 705 cm-'. Anal. Calcd for C14Hle03: C, 72.39; H, 6.94; 0, 20.67. Found: C, 72.17; H, 6.95; 0, 20.51. trans -3-Methoxy- 1-phenyl-1,5-hexadiene (27). 3Hydroxy-l-phenyl-l,5-hexadiene (26) (1.74 g, 10 mmol), dissolved in 5 mL of dry THF, was added to a well-stirred slurry of NaH (400 mg as an 80% suspension in oil 15 mmol) in 10 mL of dry THF under a nitrogen atmosphere. After stirring for 45 min, Me1 (7.1 g, 50 mmol) dissolved in 10 mL dry THF was added, and the mixture was left for 1h at ambient temperature and then heated to 40 O C overnight. The excess NaH was destroyed with 1 mL of MeOH, the mixture was concentrated in vacuo, and 100 mL of E t 2 0 was added to the concentrate. The organic phase was washed with water (2 X 20 mL) and brine (20 mL) and dried (MgS04). The solvent was removed in vacuo to yield 1.84 g of an oil. Following flash column chromatography (petroleum ether/EtzO, 7/3), 1.81 g (9.6 mmol, 96%) of 27 was obtained as a colorless oil. 27: Rf = 0.6 (petroleum ether/EhO, 7/3); 'H NMR (200 MHz) 6 7.15-7.45 (m, 5 H, Ph), 6.45 (A part of ABX, JAB = 16, Jm = 0 Hz, 1 H, PhCH=CH), 6.08 (B part of ABX, JAB = 16 and JBX = 7.5 Hz, 1 H, PhCH=CH), 5.85 (ddt, J = 17,lO and 7 Hz, 1 H, CH2=CH), 5.02-5.18 (m, 2 H, CH2=CH), 3.78 (m, 1 H,CH(OMe)), 3.33 (s, 3 H, OMe), 2.27-2.55 (m, 2 H,CHz); 13CNMR (50.3 MHz, Me4Sias internal standard) 6 136.74,134.46, 132.41, 129.86, 128.57, 127.69, 126.53, 116.98, 82.01, 56.27,40.24; IR (film) 3080,3030,2980,2930,1640,1450,1100,970,915,750, 695 cm-'. Cyclization of Compound 27. To a well-stirred solution of 27 (564 mg, 3 mmol) in 15 mL of acetic acid was added P ~ ( O A C ) ~ (33.7 mg, 0.15 mmol), Mn02 (196.8 mg, 2.26 mmol), and benzoquinone (82 mg, 0.76 mmol). The mixture was stirred for 48 h, and additional amounts of Mn02 (39.2 mg, 0.45 mmol) and benzoquinone (16.2 mg, 0.15 mmol) were added. After stirring for an additional 24 h and 30 min, brine (15 mL) was added, and the aqueous phase was extracted with petroleum ether/EhO (2 X 30 mL 8/2 and 10 mL l/l). The combined organic phase was washed with water (5 mL) and saturated aqueous Na2C03(2 X 10 mL). The combined aqueous phase was then extracted with petroleum ether/Et20 (15 mL, l / l ) , and the organic phase was washed with Na2C03(saturated). The combined organic phase was dried (MgS04),and the solvent was removed in vacuo to afford 691 mg of an oil. Flash chromatography (a stepwise gradient of
J. Org. Chem., Vol. 54, No. 20, 1989 4923 petroleum ether/EhO 19/1,9/1,4/1, and 7/3 was used) gave 27 (39 mg, 0.207 mmol), 34 (45 mg, 0.208 mmol), one fraction containing a mixture of 31a and 31b (234 mg, 0.951 mmol), and one fraction containing a mixture of 31 (57 mg, 0.232 mmol) and 35 (116 mg, 0.423 mmol). Yield of 31a/31b, 40%; ratio, 54/46. The two diastereomers were partially separated on HPLC (petroleum ether/EtOAc, 9/1) for structural determination. 31a: Rf = 0.22 (petroleum ether/EhO, 7/3); 'H NMR (200 MHz) 6 7.18-7.44 (m, 5 H, Ph), 6.58 (br s, wl12 = 6 Hz, 1 H, PhCH=C), 5.31 (m, 1 H, CHOAc), 3.42 (br s, wllz = 12 Hz, 1 H, CHOMe), 3.31 (s, 3 H, OMe), 3.05 (br dd, J = 17 and 7 Hz, 1 H, C=CCH2), 2.49 (br dd, J = 17 and 4 Hz, partially overlapping with one of CH(OMe)CH2, 1 H, C=CCH2)), 2.39 and 1.97 (AB part of ABMX, JAB= 14.5, JAM = 6, Jm = 3, JBM = 6, and JBX = 6 Hz, 2 H, CH(OMe)CH2), 2.01 (s,3H, OAc); 13CNMR (100.6 MHz) 6 170.84, 140.74, 137.04, 128.54,128.28,128.16,126.97,78.30,73.37,54.99,39.71,38.22,21.21. 31b Rf = 0.22 (petroleum ether/EhO, 7/3); 'H NMR (200 MHz) 6 7.18-7.45 (m, 5 H, Ph), 6.58 (br s, wl12 = 6 Hz, 1 H, PhCH=C), 5.13 (apparent quintet, 1 H, CHOAc), 4.30 (br t, J = 4 Hz, 1 H, CHOMe), 3.34 (s, 3 H, OMe), 2.87 and 2.79 (AB part of ABX, broadened by allylic coupling to PhCH=C, JAB= 17, J m = 6.5 Hz and JBX = 5.5 Hz, 2 H, C=CCH2), 2.1-2.25 (m, 2 H, CH(OMe)CH2),2.07 (s, 3 H, OAc); 13C NMR (100.6 MHz) 6 171.07,
140.08, 136.92, 128.54, 128.34, 128.28, 127.03, 78.23, 72.89, 54.99, 40.05, 37.23, 21.26. Cyclization of Compound 27 Using a Stoichiometric Amount of Pd(OAc)z. After a mixture of 27 (188.3mg, 1mmol) and P ~ ( O A C(224.5 ) ~ mg, 1m o l ) in 5 mL of acetic acid was stirred at ambient temperature for 72 h, 5 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (2 15 mL 7/3, 10 mL l/l). The combined organic phase was washed with water (5 mL) and saturated aqueous Na2C03(2 X 5 mL) and dried (MgS04). The solvent was removed in vacuo to give 209.2 mg of a dark oil. Flash chromatography (a stepwise gradient of petroleum ether/Et20, 9/1, 4/1,7/3, 3/2, 1/1, and ?/3 was used) gave a mixture of 31s (9.8 mg, 4%), 31b (41.8 mg, 17%), and 36 (32 mg, 13%). 36: Rf= 0.3 (petroleum ether/EhO, fJ/3);'H NMR (200 MHz) 6 7.15-7.40 (m, 5 H, Ph), 5.53 (br s, kl12= 5 Hz, 1H, CH=C), 5.44 (br s, wllz = 16 Hz, 1H, CHOAc), 4.1 (dd, J = 7.5 and 4 Hz, 1H, CHOMe), 3.58 (A part of AB, JAB = 16 Hz, 1H, PhCHJ, 3.41 (B part of AB, J = 16 Hz, 1H, PhCHJ, 3.33 ( 8 , 3 H, OMe), 2.7 (dt, J = 15 and 7.5 Hz, 1H, CH2CHOMe), 2.01 (s, 3 H, OAc), 1.74 (dt, J = 15 and 4 Hz, 1H, CHzCHOMe); 13C NMR (100.6 MHz) 6 170.94, 150.22, 138.57, 129.06, 128.44, 127.24, 126.27, 83.11, 76.12, 56.20, 36.70, 34.90, 21.19. trans-3-(Benzyloxy)-l-phenyl-1,5-hexadiene (28). This compound was prepared according to the procedure described for 27 using PhCH2Cl instead of MeI: 'H NMR (200 MHz) 6 7.19-7.45 (m, 10 H, 2 Ph), 6.55 (A part of ABX, JAB = 16, Jm = 0 Hz, 1H, PhCH=CH) 6.14 (B part Of ABX, JAB = 16 and J B ~ = 8 Hz, 1 H, PhCH=CH), 5.86 (ddt, J = 17,lO and 7 Hz, 1 H, CHz=CH), 5.0-5.17 (m, 2 H, CHz=CH),4.63 (A part of AB, JAB = 12 Hz, 1 H, CH2Ph), 4.43 (B part of AB, JAB = 12 Hz, 1 H, CH2Ph), 3.98 (apparent q, 1 H, CHO), 2.31-2.61 (m, 2 H, CH2CH=); 13CNMR (50.3 MHz, Me& as internal standard) 6 138.80,136.70,134.51,132.45,130.07,128.56,128.28,127.65,127.39, 126.55,116.98,79.71,70.21,40.39 (2 C overlapping in the aromatic region); IR (film) 3060, 3030, 2980, 1640, 1450, 1090, 1070, 970, 915, 750, 695 cm-'. Cyclization of Compound 28. Compound 28 (792.5 mg, 3 mmol) was cyclized via the procedure described for 9. After the mixture was stirred at ambient temperature for 66 h, 15 mL of brine was added, and the aqueous phase was extracted with petroleum ether/Et20 (2 X 40 mL 4/1 and 10 mL l/l). The organic phase was washed with water (5 mL) and saturated aqueous Na2C03(2 X 5 mL). The aqueous phase was then extracted with petroleum ether/EhO (15 mL l/l),and the organic phase was washed with saturated aqueous Na2C03(5 mL). The combined organic phase was dried (MgS04),and the solvent was removed in vacuo to afford a dark oil. Flash chromatography (a stepwise gradient of petroleum ether/EhO, 1/0, 19/1,9/1,4/1, and 7/3 was used) gave 28 (34 mg, 0.129 mmol), 34 (43 mg, 0.2 mmol), 32a/32b (354 mg, 1.1mmol), and one fraction containing a mixture of 32a/32b (39 mg, 0.121 mmol) together with 35 (184 mg, 0.675 mmol). Yield of 32a/32b 41% in a ratio of 57/43. The two diastereomers were partially separated on HPLC (petroleum
4924 J . Org. Chem., Vol. 54, No. 20, 1989 ether/EtpO, 9 1 ) for structural determination. 32a: Rf = 0.3 (petroleum ether/EGO, 713); 'H NMR (200 MHz) 6 7.15-7.42 (m, 10 H, 2 Ph), 6.57 (br s, wl/,= 6 Hz, 1 H, PhCH=C), 5.36 (m, 1 H, CHOAc), 4.7 (br s, wlI2 = 12 Hz, 1 H, CHOCH,Ph), 4.47 (A part of AB, JAB = 11Hz, 1H, OCH2Ph),4.43 (B part of AB, JAB = 11 Hz, 1 H, OCH,Ph), 3.11 (br dd, J = 17 and 7 Hz, 1 H, C=CCH2), 2.4-2.58 (m, 2 H, C=CCH, and CH,CH(OCH,Ph)), 1.95-2.12 (m, 1H, CH2CH(OCH2Ph)),2.02 (s,3 H, OAc); '% NMR (100.6 MHz, acetone-de) 6 170.79, 142.26, 139.26, 138.17, 129.46, 129.07,129.04, 128.90, 128.36, 128.29,127.67, 77.52,73.85,70.25, 40.51,39.47, 21.02. 32b: Rf = 0.3 (petroleum ether/Et20, 7/3); 'H NMR (200 MHz) 6 7.15-7.42 (m, 10 H, 2 Ph), 6.57 (br s, w1,, = 6 Hz, 1 H, PhCH=C), 5.16 (apparent quintet, J = 6 Hz, 1H, CHOAc), 4.56 (m, 1 H, CH(OCH,Ph)), 4.52 (A part of AB, JAB = 11 Hz, 1 H, OCH,Ph), 4.47 (B part of AB, JAB= 11 Hz, 1 H, OCH,Ph), 2.76-2.99 (m, 2 H, C=CCH2), 2.13-2.37 (m, 2 H, CH&H(OCH,Ph)), 2.05 (s, 3 H, OAC);13C NMR (100.6 MHz, acetone-d,) 6 170.87, 142.45, 139.58, 138.10, 129.46, 129.07, 129.04, 128.90,128.31,128.25,127.71,77.37,73.41,70.13,41.05,38.59,21.09. Anal. Calcd for (mixture of 32a/32b)C21H22O3: C, 78.23; H, 6.88. Found: C, 78.10; H, 6.90. trans -3-Acetoxy-l-phenyl-l,5-hexadiene (29). 3-Hydroxyl-phenyl-l,5-hexadiene (26)(1.74 g, 10 mmol) was dissolved in 12 mL of Et3N, and 3.1 mL of acetic acid anhydride was added. After addition of 4-(N,N-dimethylamino)pyridine(305 mg, 2.5 mmol) during 5 min and stirring for an additional 18 h at ambient temperature, 35 mL of methanol was added, and the mixture was stirred for another 2 h and 15 min. After the mixture was concentrated in vacuo, 100 mL of ether was added, and the organic phase was washed with water (20 mL) and saturated aqueous NaHC03 (2 X 30 mL) and dried (MgSO,). Removal of the solvent in vacuo afforded 1.935 g of a dark oil. Following flash chromatography (petroleum ether/EGO, 4/1), 1.336g (6.2 mmol, 62%) of 29 was obtained as a colorless oil. 29: Rf = 0.44 (petroleum ether/EtzO, 7/3); 'H NMR (200 MHz) 6 7.2-7.45 (m, 5 H, Ph), 6.62 (A part of ABX, JAB = 16 and J u = 0 Hz,1H, PhCH=CH), 6.15 (B part of ABX, JAB = 16 and JBX = 7 Hz, 1H, PhCH=CH), 5.79 (ddt, J = 17, 10, and 7 Hz, 1 H, CH=CH2), 5.48 (4, J = 7 Hz, 1 H, CHOAc), 5.02-5.2 (m, 2 H, CH=CH2), 2.48 (br t, J = 7 Hz,2 H, CH,), 2.08 (s, 3 H, OAc); 13C NMR (50.3 MHz, Me4Si as internal standard) 6 170.03,136.43,133.17,132.66,128.57, 127.93, 127.26,126.62, 118.0,73.72,39.14, 21.16; IR (film)3080,3060,3030, 2980, 1740, 1645, 1375, 1240, 1020, 970,920, 750, 695 cm-'. Cyclization of Compound 29. The procedure described for 28 was used for the cyclization 29 (3 mmol). After the mixture was stirred for 49 h at ambient temperature and 20 h a t 50 OC, 15 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (2 X 30 mL 7/3 and 10 mL l/l). The organic phase was washed with water (5 mL) and saturated aqueous Na2C03(2 X 10 mL). The aqueous phase was extracted with petroleum ether/EhO (15 mL 1/1), and the organic phase was washed with saturated aqueous Na2C03(5 mL). The combined organic phase was dried (MgSOI), and the solvent was removed in vacuo to afford 702 mg of a brownish oil. Flash chromatography (petroleum ether/EtzO, 7/3) gave one fraction consisting of a mixture of 29 (80 mg, 0.37 mmol) and 34 (4 mg, 0.019 mmol) and another fraction containing a mixture of 33a/33b (297 mg, 1.08mmol) and 35 (139 mg, 0.507 mmol). Compounds 33a/33b were formed in a total yield of 36% in a ratio of 52/48. The isomers were separated on HPLC (petroleum ether/EtOAc, 9/1) for structural determination. 33a: Rf = 0.14 (petroleum ether/Et20, 7/3); 'H NMR (200 MHz) 6 7.15-7.4 (m, 5 H, Ph), 6.59 (br s, w1/,= 6 Hz, 1 H, PhCH=C), 5.91 (m, 1 H, PhCH= CCHOAc), 5.3 (apparent quintet, 1H, CH,CH(OAc)CH,), 3.08 (br dd, J = 17 and 6.5 Hz, 1 H, C=CCH2), 2.58 (br d, J = 17 Hz, 1 H, C=CCHz), 2.32 and 2.15 (AB part of ABMX, JAB = 15, JAM = 6.5, J m = 5, J B M = 4, and JBX = 5.5 Hz, 2 H, CH,CH(OAc)C=C), 2.04 (s, 3 H, OAc), 1.91 ( 8 , 3 H, OAc); 13C NMR (100.6 MHz) d 170.75, 170.50, 138.32, 136.40, 128.46, 128.36, 128.14, 127.20, 72.72, 72.63, 40.51, 40.00, 21.20, 20.93. Anal. Calcd (mixture of 33a and 35) for ClGH1804:C, 70.06; H, 6.61. Found: C, 69.99; H, 6.58. 33b: R, = 0.14 (petroleum ether/EkO, 7/3); 'H NMR (200 MHz) 6 7.15-7.38 (m, 5 H, Ph), 6.60 (br s, w1 = 6 Hz, 1 H, PhCH=C), 5.77 (br d, J = 6.5 Hz, 1 H, PhCfI= CCHOAc), 5.16 (m, 1 H, CH,CH(OAc)CH,)), 2.93 (ddd, A part of AB, J = 17,6 and 2 Hz, 1 H, C=CCH2), 2.82 (br d, B part of
Antonsson e t al. AB, J = 17, 1 H, C=CCH,), 2.41 (dt, J = 15.5 and 6.5 Hz, 1 H, C=CCH(OAc)CH,), 2.1 (m, 1 H, C=CCH(OAc)CH,), 2.05 (s, 3 H, OAc), 1.98 (s, 3 H, OAc); 13C NMR (100.6 MHz) 6 170.79, 170.60, 138.59, 136.33, 128.86, 128.41, 128.20, 127.33, 72.63 (2 C), 40.54, 40.27, 21.27, 21.09. Anal. Calcd for Cl,Hl8O4: c, 70.06; H, 6.61. Found: C, 69.95; H, 6.50. cis -3-Hydroxy-l-phenyl-l$-hexadiene (37). Allyl bromide (641 mg, 5.3 mmol) dissolved in 3 mL of dry EGO was added during 10 min to magnesium turnings (386 mg, 15.9 mmol) in 3 mL of dry EGO under a nitrogen atmosphere. After the mixture was stirred at ambient temperature for 30 min, cis-3-phenyl-2p r ~ p e n a(350 l~~ mg, ~ 2.65 mmol) in 7 mL of dry EGO was added. The reaction mixture was stirred for another 3.5 h and then poured into ice/water. The aqueous phase was acidified by the addition of 2 M HCl and extracted with EGO (15 + 10 mL). The combined organic phase was dried (MgS04),and the solvent was removed in vacuo to give 422 mg of an oil. Flash chromatography (petroleum ether/Et20, 1/1)gave 406 mg (2.33 mmol, 88%) of 37: R, = 0.32 (petroleum ether/Et20, 1/11; 'H NMR (200 MHz) 6 7.2-7.4 (m, 5 H, Ph), 6.58 (d, J = 12 Hz, 1 H, PhCH=CH), 5.85 (m, 1H, CH*H), 5.69 (dd, J = 12 and 9 Hz, 1H, PhCH=CH), 5.11-5.23 (m, 2 H, CH,=CH), 4.62 (m, 1 H, CHOH), 2.4 (m, 2 H, =CHCH,), 1.7 (d, J = 4 Hz, 1H, OH); "C NMR (100.6 MHz) 6 136.50, 133.95, 133.54, 131.38, 129.74,128.27,127.27,118.37,66.83, 42.06. Cyclization of Compound 37. The reaction was performed on a 1-mmol scale according to the procedure described for 9. Workup was done according to the procedure described for 26. Flash chromatography (a stepwise gradient of petroleum ether/EbO, 7/3,3/2,1/1,2/3, and 317 was used) gave 31 mg (0.14 mmol, 14%) of 30a/30b (ratio 85/15) and 50.1 mg (0.22 mmol, 22%) of 38a/38b (ratio 74/26). 38a: R, = 0.1 (petroleum ether/EGO, 2/31; 'H NMR (200 MHz) 6 7.2-7.4 (m, 5 H, Ph), 6.63 (9,J = 2.6 Hz, 1H, PhCH=C), 5.40 (m, 1H, CHOAc), 4.83 (m, 1H, CHOH), 3.20 (br dd, J = 18 and 7 Hz, 1 H, C=CCH2), 2.68 (br d, J = 18 Hz, 1 H, C=CCH,), 2.1-2.2 (m, 1 H, CH(0Ac)CH,CHOH), 2.02 (s, 3 H, OAc), 1.88-2.02 (m, 1 H, CH(0Ac)CH,CHOH), 1.69 (d, J = 5.5 Hz, 1H, OH); 13CNMR (100.6 MHz) 6 170.74, 143.55, 137.01, 128.43 (2 C), 127.00, 12495, 76.10, 73.60, 40.57, 36.37, 21.19. 38b: R, = 0.1 (petroleum ether/EtzO, 2/3); 'H NMR (200 MHz, in mixture with 38a)6 7.2-7.4 (m, 5 H, Ph), 6.73 (m, 1 H, PhCH=C), 5.27-5.4 (m, 1 H, CHOAc), 4.66 (m, 1 H, CHOH), 2.99 (ddd, part of AB, J = 18.6 and 3 Hz, 1 H, C=CCH2), 2.88 (br d, part of AB, J = 18.6 Hz, 1 H, C=CCH2), 2.05 (s, 3 H, OAc), 1.9-2.35 (m, 3 H, CH, and OH). Cyclization of trans-I-Hydroxy-1,5-heptadiene (39).% The procedure described for 9 was used for the cyclization of the alcohol 39 (561 mg; 5 mmol). After 48 h at ambient temperature, 25 mL of brine was added, and the solution was extracted with petroleum ether/EhO (2 X 125 mL 7/3,2 X 125 mL l/l), The combined organic phase was washed with a saturated aqueous solution of NaHC03 (4 X 125 mL) and dried (MgS04),and the solvent was removed in vacuo to yield 634 mg (75%) of a black liquid. The crude mixture was purified by flash chromatography (a stepwise gradient of petroleum ether/EGO, 4/1 and 312, was used) to afford 0.46 g of a mixture the alcohols 40a-d (41%) and 41 (10%). The cyclic products 40a-d and the diacetate 41 were formed in a ratio of 80/20. The diastereomers 40a-d were formed in unequal amounts (two major diastereomers 40a and 40b two minor diastereomers 40c and 40d) and were separated on HPLC (eluting with a 7/3 mixture of hexane/EtOAc). 40a: 'H NMR (200 MHz) d 5.92 (ddd, J = 17, 10.5 and 6.5 Hz, 1 H), 5.09-5.39 (m, 3 H, CH=CH,, CHOAc), 4.21-4.35 (m, 1H, CHOH), 2.68-2.90 (m, 1H), 2.02 (s, 3 H), 1.66-2.36 (m, 5 H). 40b: 'H NMR (200 MHz) 6 5.79 (ddd, J = 17, 10.5, and 6.5 Hz, 1 H), 5.0-5.28 (m, 3 H), 3.96-4.12 (m, 1H), 2.22-2.51 (m, 1H), 2.04 (s,3 H), 1.72-2.22 (m, 5 H). 40c: 'H NMR (200 MHz) 6 5.98 (ddd, J = 17,10.5 and 6 Hz, 1 H), 5.04-5.30 (m, 3 H), 4.09-4.21 (m, 1 H), 2.39-2.62 (m, 1 H); 2.04 (s, 3 H), 1.70-2.42 (m, 5 H). 4Od: 'H NMR (200 MHz) d 5.75 (ddd, J = 17, 10 and 7.5 Hz,1 H), 5.0-5.28 (m, 3 H), 3.89 (9, J = 7 Hz, 1 H), 2.40-2.74 (m, 1 H), 2.02 (s, 3 H), 1.45-2.19 (m, 5 H). 41: 'H NMR (200 MHz) 6 6.13-6.35 (m, 2 H), 5.60-5.92 (m, 2 H), 5.39 (quintet, J = 6.5 Hz,1H, CHOAc), 4.60 (d, J = 6 Hz, 2 H, CH,), 2.07 (s, 3 H), 2.05 (s, 3 H), 1.32 (d, J = 6.5 Hz, 3 H); 13C NMR (100.6 MHz) 6 170.71, 170.24, 133.80, 133.11, 130.28, 127.70, 70.34, 64.43, 21.29, 20.90, 20.11.
Palladium-Catalyzed Oxidative Cyclization
2-Methy1-2,6-heptadien-4-01(42).Allyl bromide (4.3 mL, 50 mmol) was converted into its corresponding Grignard reagent according to a previously described procedure5' except that the bromide was added over only 1 h. The Grignard solution was heated to reflux for 1 h and then transferred to another flask. Freshly distilled 3-methylbutenal(l.9 mL, 20 mmol) in dry EhO was added dropwise to the Grignard reagent over 10 min. After stirring overnight, the reaction mixture was poured onto 25 mL of ice, the white precipitate was removed by careful addition of 2 M hydrochloric acid, the two phases were separated, and the aqueous layer was extracted with EhO (3 X 25 mL). The combined organic phase was dried (MgS04),concentrated in vacuo, and purified by Kugelrohr distillation (0.15 Torr, 100 "C) to give 1.3 g (52%) of 42 as a colorless liquid: 'H NMR (200 MHz) 6 5.665.91 (m, 1H), 5.0-5.22 (m, 3 H), 4.41 (dt, J = 9 and 6.5 Hz, 1 H), 2.28 (t, J = 6.5 Hz, 2 H), 1.70 (8, 3 H), 1.68 (9, 3 H), 1.65 (9, 1 H). Oxidation of Compound 42. The alcohol 42 (630 mg; 5.0 mmol) was treated in the same way as 39, except that a higher temperature was used (50 "C for 8 h). Brine (25 mL) was added, and the solution was extracted with petroleum ether/EkO (2 X 125 mL 7/3,2 X 125 mL, l/l).The combined organic phase was washed with a saturated aqueous solution of NaHC03 (4 x 25 mL) and dried (MgS04),and the solvent was removed in vacuo to yield 0.78 g (85%) of a black liquid. The crude mixture was purified by flash chromatography (a stepwise gradient of petroleum ether/EhO, 9/1 and 2/3, was used) to afford 0.36 g (39%) of a mixture of the alcohols 43 and 44 in a ratio of 60/40. The ratio 44a/b was 40/60 by 'H NMR. The diastereomers were separated on HPLC (eluting with a 4/1 mixture of hexane/EtOAc). 4 3 'H NMR (200 MHz) 6 5.81 (ddt, J = 17,lO and 7 Hz, 1 H), 5.49 (dd, J = 8.5 and 1Hz, 1 H), 5.05-5.24 (m, 2 H), 4.46 (br s, 3 H, CH20Ac, CHOH), 2.30 (t, J = 7 Hz, 2 H, CH2),2.05 (s,3 H, OAc), 1.73 (s,3 H, CHd, 1.65 (9, 1H, OH); '9c NMR (100.6 MHz) 6 170.74, 133.92, 132.58, 130.21, 118.15, 68.91,67.19,41.76, 20.81, 14.25. 44a: 'H NMR (400 MHz) 6 5.78 (ddt, J = 17, 10, and 7 Hz, 1 H), 4.94-5.08 (m, 5 H, 2 =CH2, CHOAc), 4.20 (br t, J = 4 Hz, 1H), 2.362.42 (m, 2 H, CHJ, 2.06 (s,3 H, CH3COO), 1.92 (d, J = 4 Hz, 1H, OH), 1.55 ( 8 , 3 H, CH3). 44b: 'H NMR (400 MHz) 6 5.85 (ddt, J = 17, 10, and 7 Hz, 1H), 5.12-5.17 (m, 2 H), 5.09 (d, J = 5.3 Hz, 1H, CHOAc), 5.02-5.04 (m, 2 H), 3.82 (ddt, J = 4.5, 5.3, and 7 Hz, 1 H), 2.17-2.32 (m, 2 H), 2.13 ( 8 , 3 H), 1.90 (d, J = 4.5 Hz, 1H), 1.78 (s,3 H); 13CNMR (100.6 MHz) 6 170.18, 140.92, 133.87, 118.33, 114.45, 79.11, 70.35, 37.52, 21.03, 19.23. Oxidation of Compound 45.@ The diene 45 (611 mg,5 mmol) was treated in the same way as 42. After the addition of brine the solution was extracted with petroleum ether/EhO (3 X 125 mL 4/1, 2 X 125 mL 7/3). The combined organic phase was washed with a saturated aqueous solution of NaHC03 (4 X 125 mL) and dried (MgS04),and the solvent was removed in vacuo to yield 1.0 g of a black liquid. The crude mixture was dissolved in 25 mL of E g o , washed with saturated NaHC03 (3 X 10 mL), and dried (MgS04),and the solvent was removed in vacuo to yield 0.43 g (47%) of a mixture of 46 and 47. The crude mixture was purified by flash chromatography (a stepwise gradient of petroleum ether/EhO, 9/1 and 1/1,was used) to afford 0.26 g (29%) of a mixture of the acetates 46 and 47, by GLC in a ratio of 80/20, together with minor amounts of unidentified products. The products were separated by HPLC (eluting with a 99/1 mixture of hexane/EtOAc). 46: 'H NMR (200 MHz) 6 5.56-5.92 (m, 3 H), 5.20-5.36 (m, 1 H), 4.92-5.10 (m, 2 H), 2.14-2.32 (m, 2 H), 2.05 (9, 3 H), 1.80-1.96 (m, 2 H), 1.48-1.69 (m, 1 H), 1.20-1.45 (m, 2 H); 13CNMR (100.6 MHz) 6 170.84, 136.32,135.64, 126.44, 116.45, 69.53, 39.83, 34.85, 27.48, 26.15, 21.37. 4 7 'H NMR (200 MHz) 6 5.62-5.95 (m, 3 H), 5.20 (br q, J = 4 Hz, 1 H, CHOAc), 4.92-5.14 (m, 2 H), 2.05 (s, 3 H), 1.92-2.18 (m, 3 H), 1.54-1.92 (m, 3 H), 1.32-1.59 (m, 1 H); 13C NMR (100.6 MHz) 6 170.77, 136.62,133.08,125.0,116.23,68.64,37.34,35.72,25.32,23.85,21.16.
(57) Benkeser, R. A. Synthesis 1971,347. (58) Bartlett, P. D.; Nicholson, E. M.; Owyang, R. Tetrahedron 1966, Suppl. 8, Part 11, 399.
J. Org. Chem., Vol. 54,No. 20,1989 4925 Cyclization of 6-(2-Ethenyl)-2,8-nonadienyl Acetate (48).69 This reaction was run on a 2.52-mmol scale according to the procedure described for 9. After the mixture was stirred for 40 h at 20 "C, 13 mL of brine was added, and the aqueous phase was extracted with 4 X 15 mL of pentane/ether. The combined organic phase was washed with water (1 X 5 mL) and saturated aqueous Na&03 (2 X 5 mL) and dried (MgSOS. The solvent was removed in vacuo to afford 604 mg of an oil. Following flash chromatography(using a stepwise gradient of pentane/EkO, 3/1 and 7/3), a mixture of 49a and 49b (54%) together with some unidentified acetates (18%) was obtained (ratio of 49a/49b = 33/67). The two diastereomers were separated by HPLC (hexane/EtOAc, 19/1) for structural determination. 49a: Rf = 0.35 (pentane/EhO, 7/3); 'H NMR (200 MHz) 6 5.78 (dt, part of AB, J = 16 and 6.5 Hz, 1 H, CH=CHCH,OAc), 5.60 (dt, part of AB, J = 16 and 6.5 Hz, 1H, C H ~ H C H ~ O A C 5.07 ) , (quintet, J = 6.5 Hz, 1 H, CHOAc), 4.83-4.94 (m, 2 H, C H d ) , 4.51 (d, J = 6.5 Hz, 2 H, CH20Ac), 2.72-2.80 (m, 1H, CH2=CHH2), 2.36-2.44 (m, 1H, CH,==CCHJ, 2.25-2.34 (m, 1H, CH(OAc)CH,CH), 2.07 (s, 3 H, CH20Ac), 2.03 (9, 3 H, CHOAc), 2-2.2 (m, 3 H, CHCH2CH2CH=),1.72-1.81 (m, 1H, CH2CH2CH=), 1.39-1.48 (m, 2 H, CHzCH2CH= and CH(OAc)CH2CH);13CNMR (100.6 MHz) 6 170.7 (2 C) 152.00, 135.59, 124.32, 106.55, 73.99, 65.10, 41.17, 39.51, 37.88, 33.93, 30.29, 21.16, 20.93. Anal. Calcd for C15H2204: C, 67.62; H, 8.33. Found: C, 67.51; H, 8.26. 49b: R, = 0.35 (pentane/EkO, 7/3); 'H NMR (200 MHz) 6 5.80 (at,part of AB, J = 15.5 and 6.5 Hz,1H, CH=CHCH,OAc), 5.60 (dt, part of AB, J = 15.5 and 6.5 Hz, 1 H, CH=CHCH,OAc), 5.19 (tt, J = 5 and 2.5 Hz, 1H, CHOAc),4.85-4.98 (m, 2 H, CH,=C), 4.52 (dd, J = 6.3 and 0.84 Hz,2 H, CH20Ac),2.67 (m, part of AB, JAB = 17 Hz, 1 H, CH2=CHH2), 2.6 (m, 1 H, CH2=CCH),2.46 (m, part Of AB, J A B = 17 Hz,1H, CH*CHJ, 2.07 ( ~ , H, 3 CH~OAC), 2.02 (s,3 H, CHOAc), 2-2.2 (m, 3 H, one of CH(OAc)CH2CHand CH2CH=CHCH20Ac),1.67-1.87 (m, 1H, CH2CH2CH=CH),1.54 (ddd, J = 14,lO and 5 Hz, 1H, CH(OAc)CH,CH), 1.35 (m, 1H, CH2CH,CH=CH); 13CNMR (100.6 MHz) 6 170.76,170.72,152.67, 135.85,124.25,106.32,74.50,65.10,40.87,39.82,38.64,33.44,30.24, 21.26,20.93. Anal. Calcd for C15HBO4: C, 67.62; H, 8.33. Found C, 67.47; H, 8.20. trans -3-(o-Hydroxyalkoxy)-l-phenyl1,5-hexadienes (53-55). To a slurry of fiiely powdered KOH (4.48 g, 80 mmol) in 34 mL of dry DMSO was added trans-3-hydroxy-1-phenyl1,5-hexadiene (26) (3.48 g, 20 mmol) dissolved in 6 mL of dry DMSO and the appropriate w-chloro alcohol tetrahydropyranyl ether (40 mmol). After the mixture was stirred at 40 O C for 20 h, water (100 mL) was added, and the aqueous phase was extracted with EhO (100 mL and 2 X 50 mL). The combined organic phase was washed with water (2 X 25 mL) and brine (25 mL) and dried (MgS04). Removal of the solvent and the excess tetrahydropyranyl ether in vacuo (bulb-to-bulb apparatus, 100 "C ca. 0.5 Torr) afforded an oil. Following flash chromatography (using a stepwise gradient of petroleum ether/EhO, 9/1,4/1, 7/3, 3/2, and 1/1)50 (67%), 51 (34%), and 52 (91%), respectively, were obtained. 5 0 Rf = 0.58 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.2-7.45 (m, 5 H, Ph), 6.55 (A part of ABX, JAB = 16 and Jm = 0 Hz, 1H, PhCH=CH), 6.10 (B part of ABX, J A B = 16 and Jax = 8 Hz,1H, PhCH=CH), 5.86 (m, 1H, CH.+H), 5.0-5.16 (m, 2 H, CH2=CH),4.61 (br t, J = 3 Hz, 1H, OCHO), 3.42-4.02 (m, 7 H, CHOCH2CH20CHOCH2),2.262.58 (m, 2 H, CH2=CHCH2), 1.4-1.9 (m, 6 H, OCH,CH2CH,CH&. 51: Rf = 0.58 (petroleum ether/EhO, 2/3); lH N M R (200 M H z ) 6 7.17-7.42 (m, 5 H, Ph), 6.52 (A part of ABX, JAB = 16 and Jm= 0 Hz, 1 H, PhCH=CH), 6.08 (B part of ABX, JAB = 16 and JBX= 8 Hz, 1H, PhCH=CZf), 5.85 (ddt, J = 17,10, and 7 Hz,1H, C H + 2 H ) , 5.0-5.16 (m, 2 H, C H d H ) , 4.57 (m, 1H, OCHO), 3.36-3.93 (m, 7 H, CHOCHzCHzCH20CHOCHJ,2.39 (m, 2 H, C=CCH2), 1.87 (quintet, J = 6 Hz, 2 H, OCH2CH2CH20),1.4-1.9 (m, 6 H, CH2CH2CH2CH20).52: Rf = 0.58 (petroleum ether/EhO, 2/3); 'H NMR (200 M H z ) 6 7.19-7.44 (m, 5 H, Ph), 6.52 (A part of ABX, J A B = 16 and Jm = 0 Hz,1H, PhCH=CH), 6.09 (B part of ABX, J A B = 16 and JBx = 7.8 Hz, 1H, PhCH=CH), 5.86 (ddt, J = 17, 10 and 7 Hz, 1H, CH2=CH), 5.01-5.16 (m, 2 H, CH2=CH),4.57 (m, 1H, OCHO), 3.86 (apparent q, 1H, CHOCH2CH2CHz0CHO), (59) Antonsson, T.; Moberg, C. Organometallics 1985, 4 , 1083.
Antonsson e t al.
4926 J. Org. Chem., Vol. 54, No. 20, 1989 3.4-3.9 (m, 6 H, OCH2CH2CH2CH20CHOCH2),2.26-2.55 (m, 2 H, C=CCH& 1.4-1.9 (m, 10 H, pyranyl and OCH&H2CH&H20). To a solution of the appropriate tetrahydroparanyl ether (50-52) in MeOH (8 mL per mmol substrate) was added p-TsOH (0.05 equiv), and the mixture was stirred at ambient temperature for 1 h. After removal of MeOH in vacuo, EhO (150 mL) was added, and the organic phase was washed with saturated aqueous NaZCO3and dried (MgSO,). Removal of the solvent in vacuo afforded an oil. Following flash chromatography (petroleum ether/EhO, 1/1, for 53 and 55 and a stepwise gradient of petroleum ether/EhO, 2/3 and 1/4, for 54) 53 (81%),54 (82%), and 55 (65%) were obtained as colorless oils. 53: Rf = 0.26 (petroleum ether/EkO, 2/3); 'H NMR (200 MHz) 6 7.2-7.45 (m, 5 H, Ph), 6.54 (A part of ABX, JAB = 16 and Jm 0, 1 H, PhCH=CH), 6.09 (B part of ABX, JAB = 16 and JBX = 8 Hz, 1 H, PhCH=CH), 5.85 (ddt, J = 17,lO and 7 Hz, 1H, C H f l H ) , 5.03-5.19 (m, 2 H, C H 2 4 H ) , 3.93 (apparent q, 1 H, CHO), 3.61-3.79 (m, 3 H, OCH2CH20H), 3.40-3.55 (m, 1 H, OCH2CH20H),2.29-2.56 (m, 2 H, CH2=CHCH2), 2.0 (t, J = 6 Hz, 1 H, OH); 13C NMR (50.3 MHz) 6 136.54, 134.38, 132.33, 129.79, 128.56,127.76,126.52,117.23,80.77,69.73,61.92,40.25;
IR (film)3600-3160,3080,3030,2980,2940,2860,1640,1150,1065, 970,915,750,and 695 cm-'. 5 4 Rf = 0.26 (petroleum ether/&O, 2/3); 'H NMR (200 MHz) d 7.2-7.43 (m, 5 H, Ph), 6.53 (A part of ABX, JAB = 16 and Jm z 0 Hz,1H, PhCH=CH), 6.08 (B part of ABX, JAB = 16 and J B X = 8 Hz, 1H, PhCH=CH), 5.84 (ddt, J = 17,10, and 7 Hz, 1 H, CH2=CH), 5.04-5.18 (m, 2 H, CH? CH), 3.90 (apparent q, 1 H, CHO), 3.71-3.83 (m, 3 H, OCH2CH2CH20H),3.45-3.56 (m, 1H, OCH2CH2CH20H),2.45 (t, J = 5.5 Hz, 1 H, OH), 2.28-2.53 (m, 2 H, C=CCH2), 1.83 (quintet, J = 5.5 Hz, 2 H, CHzCH2CH2);13C NMR (50.3 MHz) 6 135.94,133.76,131.79,129.26,128.07,127.25,126.02,116.87,80.52, 67.44,61.57,40.40,32.32;IR (film)3600-3200,3070,3060,3030, 2930,2860,1640,1190-1170,970,915,750,695 cm-'. 55: Rf = 0.24 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.2-7.43 (m, 5 H, Ph), 6.53 (A part of ABX, JAB= 16 and J m = 0 Hz, 1 H, PHCH=CH, 6.09 (B part of ABX, JAB= 16 and JBX = 7.9 Hz, 1 H, PhCH=CH), 5.84 (ddt, J = 17, 10 and 7 Hz, 1 H, C H + 2 H ) , 5.02-5.17 (m, 2 H, CH2=CH), 3.89 (apparent q, 1H, CHO), 3.65 (m, 2 H, CH20H),3.59 (A part of ABX2, JAB= 9.5 and J f i = 6 Hz, 1H, ROCHZ), 3.48 (B part of ABX2, JAB= 9.5 and J B X = 6 Hz, 1H, ROCH2),2.27-2.56 (m, 3 H, C=CCH2and OH), 1.62-1.73 (m, 4 H, OCH2CHzCH2CH20);13CNMR (100.6 MHz) 6 136.45, 134.25, 132.24, 129.86, 128.54, 127.70, 126.46, 117.17, 80.68, 68.47, 62.64, 40.23, 30.21, 26.77. trans -3-(~-Cyanoalkoxy)-1-phenyl-lP-hexadienes 59-6 1. p-Toluenesulfonyl chloride (1.1equiv) was added during 10 min to a well-stirred solution of the appropriate alcohol (53-55) in dry pyridine (0.3 mL per mmol) at 0 OC. After the mixture had been stirred for an additional 4 h a t 0 "C, 2 M HCI (3 mL/mmol substrate) was added, and the aqueous phase was extracted with Et20. The combined organic phase was washed with saturated aqueous Na2C03and dried (MgS04). Removal of the solvent in vacuo gave 56 (95%), 57 (93%), and 58 (98%), respectively. 56: lH NMR (200 MHz) 6 7.79 (d, J = 8.5 Hz, 2 H, p-tolS03)7.2-7.4 (m, 7 H, p-tolS03 and Ph), 6.48 (A part of ABX, JAB= 16 and Jm =z 0 Hz, 1 H, PhCH=CH), 5.98 (B part of ABX,JAB= 16 and JBx = 8 Hz, 1 H, PhCH=CH), 5.76 (ddt, J = 17,lO and 7 Hz,1H, CH&H), 4.98-5.12 (m, 2 H, CH&H), 4.16 (apparent t, 2 H, CH2CH20S02R),3.85 (apparent q, 1 H, CHO), 3.49-3.75 (m, 2 H, OCH2CH20S02R),2.42 (s, 3 H, Me), 2.33 (m, 2 H, C=CCH2). 57: 'H NMR(200 MHz) 6 7.77 ( d , J = 8.5 H z , 2 H, p-tolSOd, 7.2-7.4 (m, 7 H, p-tols03and Ph), 6.48 (A part of ABX, JAB = 16 Hz and Jm = 0 Hz, 1 H, PhCH=CH), 6.0 (B part of ABX, JAB = 16 and J s x = 7.8 Hz, 1H, PhCH=CH), 5.75 (ddt, J = 17,10, and 7 Hz, 1 H, CH2=CH),4.87-5.11 (m, 2 H, CH2= CH), 4.07-4.24 (m, 2 H, p-tolS020CH2),3.97 (apparent q, 1 H, CHO), 3.55 (A part of ABX2, JAB= 9.7 and J m = 6 Hz, 1 H, CHOCH&H,), 3.35 (B part of ABX2, JAB= 9.7 and JBX = 6 Hz, 1 H,CHOCH2CH,), 2.18-2.45 (m, 2 H,C=CCH2), 2.42 (s,3 H, Me), 1.90 (quintet, J = 6 Hz, 2 H, CH2CH2CHz).58: 'H NMR (200 MHz) 6 7.78 (d, J = 8.4 Hz, 2 H, p-tolSO,), 7.2-7.42 (m, 7 H, p-tolSOs and Ph), 6.49 (A part of ABX, JAB= 16.2 and JAx = 0 Hz, 1 H, PhCH=CH), 6.04 (B part of ABX, JAB = 16.2 and J B X = 7.7 Hz, 1H, PhCH=CH), 5.80 (ddt, J = 17,10, and 7 Hz, 1 H, CH2=CH), 5.0-5.14 (m, 2 H, CH2=CH), 4.06 (t, J = 6.3 Hz,
2 H, CH20SOz-p-tol),3.8 (m, 1 H, CHO), 3.49 (A part of ABX2, = 9.5 and Jm = 6 Hz, 1 H, CHOCH2) 3.28 (B part of ABX2, JAB= 9.5 and J B X = 6 Hz, 1 H, CHOCH,), 2.43 (s, 3 H, Me), 2.1-2.49 (m, 2 H, C=CCH2), 1.5-1.84 (m, 4 H, OCH2CHzCH2CH2CN). To a solution of the appropriate tosylate (56-58) in dry DMSO (3 mL/mmol substrate) was added NaCN (1 equiv), and the mixture was stirred for 19 h at ambient temperature. After addition of water and brine the aqueous phase was extracted with EhO. The combined organic phase was washed with water and brine and dried (MgSO,). The solvent was removed in vacuo to give an oil. Flash chromatography (a stepwise gradient of petroleum ether/EhO, 4/1 and 3/2, was used) gave 59 (go%),60 (96%), and 61 (99%), respectively. 59: R f = 0.48 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz), 6 7.2-7.43 (m, 5 H, Ph), 6.56 (A part of ABX, JAB = 16 and Jm 0 Hz,1H, PhCH=CH), = 8 Hz, 1H, PhCH=CH), 6.07 (B part of ABX, JAB = 16 and JBX 5.85 (ddt, J = 17,10, and 7 Hz, 1 H, CH2=CH), 5.03-5.18 (m, 2 H, CH2=CH), 3.94 (apparent q, 1 H, CHO), 3.76 (A part of ABX2, JAB = 9.5 Hz, Jm = 6.4 Hz, 1 H, OCHZCH2CN), 3.58 (B part of ABX2, J A B = 9.5 HZand Jm = 6.4 Hz, 1H, OCH&H&N), 2.59 (t,J = 6.4 Hz, 2 H, CHzCN),2.28-2.54 (m, 2 H, C=CCH2); 13CNMR (50.3 MHz, Me4Sias internal standard) 6 135.45,133.20, 132.18, 128.25,127.89, 127.23, 125.85, 117.17, 116.72,80.78,62.71, 39.97,18.93; IR (film) 3080,3060,3030,2980,2250,1640, 1100, 975, 920, 755, 695 cm-'. 6 0 Rf = 0.52 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.17-7.43 (m, 5 H, Ph), 6.53 (A part of ABX, JAB = 16 and Jm = 0 Hz,1H, PhCH=CH), 6.06 (B part of ABX, JAB = 16 and J B X = 7.8 Hz, 1H, PhCH=CH), 5.83 (ddt, J = 17,lO and 7 Hz, 1 H, CH,=CH), 5.01-5.17 (m, 2 H, CH2= CH), 3.87 (apparent q, 1H, CHO), 3.65 (A part of ABX,, JAB= 9.7 and JAY = 6 Hz,1 H, CHOCH2CH2),3.42 (B part of ABX2, JAB= 9.7 and J B X = 6 Hz, 1 H, CHOCHzCH2),2.26-2.53 (m, 4 H, C=CCH2 and CH2CN), 1.9 (quintet, J = 6 Hz, 2 H, CH2CH2CH2); I3C NMR (50.3 MHz, Me4Si as internal standard) 6 136.49, 134.28, 132.31, 129.71, 128.56, 127.76, 126.51, 119.41, 117.11,80.67,65.83,40.21, 26.00, 14.6; IR (film) 3080, 3060,3030, 2940,2250,1640,1100,970,920,750,695cm-'. 61: 'H NMR (200 MHz) 6 7.2-7.43 (m, 5 H, Ph), 6.52 (A part of ABX, JAB= 16 and = 16.0 Jm 0 Hz, 1H, PhCH=CH), 6.07 (B part of ABX, JAB and JBX = 7.8 Hz, 1 H, PHCH==CH), 5.84 (ddt, J = 17,lO and 7 Hz, 1 H, CH2=CH), 5.08-5.17 (m, 2 H, CH,=CH), 3.85 (ap= 9.6 and J m parent q, 1H, CHO), 3.58 (A part of ABX2, JAB = 5.7 Hz, 1 H, CHOCH,), 3.36 (B part of ABX2, JAB= 9.6 and J B X = 5.9 Hz,1 H, CHOCHZ), 2.25-2.53 (m, 2 H, C=CCHJ, 2.38 (t, J = 7 Hz, 2 H, CH2CN), 2.64-2.85 (m, 4 H, CH2CH2CH2CH,CN);13C NMR (100.6 MHz) 6 136.44, 134.41, 132.16,129.92, 128.58, 127.74, 126.46, 119.69, 117.06,80.57,67.22, 40.28, 28.68, 22.67, 16.96. trans -3-(Carboxya1koxy)-1-phenyl-1P-hexadienes 62-64.60 To a solution of pyridinium dichromate (3 equiv) in dry DMF (0.6 mL per mmol substrate) was added the appropriate alcohol (53-55) dissolved in 2 mL of dry DMF. After the mixture was stirred a t ambient temperature for 18 h and water was added, the aqueous phase was extracted with EhO. The organic phase was washed with water and extracted with aqueous saturated Na2C03. The basic aqueous phase was acidified by addition of 2 M HC1 and then extracted with EhO. After drying (MgSO,) and removal of the solvent in vacuo 62 (46%), 63 (26%), and 64 (66%) were obtained as colorless oils. 62: 'H NMR (200 MHz) 6 7.21-7.43 (m, 5 H, Ph), 6.57 (A part of ABX, JAB= 16 and Jm = 0 Hz, 1 H, PhCH-CH), 6.05 (B part of ABX, JAB= 16 and JBx = 8 Hz, 1 H, PhCH=CH), 5.86 (ddt, J = 17, 10, and 7 Hz, 1 H, CH2=CH), 5.08-5.23 (m, 2 H, CH2=CH), 4.18 (A part of = 16.5 Hz, 1 H, CH,COOH), 4.05 (B part of AB, JAB = AB, JAB 16.5 Hz, 1 H, CH,COOH), superimposed on 3.97-4.1 (m, 1 H, CHO), 2.36-2.64 (m, 2 H, C=CCH2);13CNMR (50.3 MHz, Me4Si as internal standard) 6 173.81,135.19,133.26,132.98,127.87,127.38, 127.20,125.90,117.04,81.11,64.75,39.81. 6 3 'H NhEt (200 MHz) 6 7.2-7.43 (m, 5 H, Ph), 6.55 (A part of ABX, JAB = 16 and J a =z 0 Hz,1 H, PhCH=CH), 6.08 (B part of ABX, JAB = 16 and JBx = 7.5 Hz, 1 H, PhCH=CH), 5.83 (ddt, J = 17, 10, and 7.5 Hz,1H, CH,==CH), 5.02-5.16 (m, 2 H, CH2=CH), 3.92 (apparent JAB
(60)Corey, E.J.; Schmidt, G. Tetrahedron Lett. 1979,20, 399.
Palladium-Catalyzed Oxidative Cyclization q, 1 H, CHO), 3.83 (A part of ABX2, JAB = 9.5 and Jm = 6 Hz, 1H, OCH&HpCOOH), 3.64 (B part of AB& JAB = 9.5 and JBX = 6 Hz,1H, OCH2CHzCOOH), 2.64 (t,J = 6 Hz,2 H, CH&OOH), 2.26-2.54 (m, 2 H, C=CCHz); 13C NMR (100.6 MHz) 6 176.96, 136.39, 134.19,132.47,129.44,128.57, 127.79,126.53,117.23,81.01, 63.57, 40.19, 34.97. 64: 'H NMR (200 MHz) 6 7.18-7.42 (m, 5 H, Ph), 6.51 (A part of ABX, J A B = 16 and J M e 0 Hz, 1 H, PhCH=CH), 6.06 (B part of ABX, JAB = 16.0 and JBX = 7.8 Hz, 1H, PhCH=CH), 5.83 (ddt, J = 17,10, and 7 Hz,1H, CH-yCH), 5.0-5.15 (m, 2 H, CH2=CH), 3.85 (m, 1 H, CHO), 3.58 (A part of ABX2,JAB = 9.5 and Jm = 6.0 Hz, 1 H, CHOCH,), 3.37 (B part of ABX2, J A B = 9.5 and JBx = 6.0 Hz, 1 H, CHOCH,), 2.46 (t, J = 7.3 Hz, 2 H, CH2COOH),2.25-2.52 (m, 2 H, C=CCH2), 1.89 (m, 2 H, CH2CH2COOH);13C NMR (100.6 MHz), 6 179.27, 136.51, 134.38, 132.19,129.92, 128.57,127.71,121.50,117.09,80.56, 67.20, 40.25, 31.09, 24.88. Cyclization of trans -3-(2-Hydroxyethoxy)-l-phenyl-1,5hexadiene (53). This compound (2 mmol) was reacted according to the procedure described for 9. After the mixture was stirred for 67 h at ambient temperature, 10 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (3 X 20 mL 2/3). The combined organic phase was washed with water (5 mL) and saturated aqueous Na2C03(4 X 5 mL). The combined aqueous phase from the wash was then extracted with petroleum ether/EhO (25 mL 2/3), and the organic phase was washed with saturated aqueous NazC03(2 X 5 mL). After drying (MgS04)and removal of the solvent in vacuo, 535 mg of an oil was obtained. Flash chromatography (a stepwise gradient of petroleum ether/E&O, 2/3,1/9, was used) gave 34 (33.9 mg,0.157 mmol), 35 (112.3 mg, 0.41 mmol), and 65a/65b (256 mg, 0.926 mmol). Yield of 65a/65b: 46%, ratio 60/40. The two diastereomers were separated by HPLC (petroleum ether/EtOAc, 3/2) for structural determination. 65a: Rf = 0.12 (petroleum ether/EtzO, 2/3); 'H NMR (200 MHz) 6 7.17-7.5 (m, 5 H, Ph), 6.58 (br s, wl12 = 6 Hz, 1H, PhCH=C), 5.31 (m, 1 H, CHOAc), 4.67 (m, 1 H, CHOCH,), 3.4-3.8 (m, 4 H, OCH,CH,OH), 3.05 (br dd, J = 17 and 6.5 Hz, 1 H, C=CCH2), 2.51 (br d, J = 17 Hz, 1 H, C=CCH2), 2.41-2.26 (ddd, part of AB, J = 14.6,6, and 3.5 Hz, 1H, CH(0Ac) CH2CHO),1.97-2.15 (m, 1H, CH(OAc)CH2CHO), 2.02 (8, 3 H, OAc), 1.73 (t,J = 6.2 Hz, 1H, OH); '% NMR (100.6 MHz, acetone-d,) 6 170.80,142.29,138.18,129.55,129.06,128.32, 127.66, 77.98, 73.84, 70.12,61.94,40.47,39.40, 21.01. 65b: Rf = 0.12 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.18-7.43 (m, 5 H, Ph), 6.58 (br s, wIl2 = 6 Hz, 1 H, PhCH=C), 5.22 (m, 1 H, CH(OAc)), 4.53 (br d, J = 5 Hz, 1 H, CHOCH2),3.5-3.85 (m, 4 H, OCH,CH,OH), 2.92 (ddd, part of AB, J = 17.5,6.5, and 2 Hz, 1 H, C=CCH2), 2.82 (br d, part of AB, J = 17.5 Hz, 1H, C=CCH2),2-2.33 (m, 3 H, OH and CH(OAc)CH2CHO),2.07 (8, 3 H, OAc); 13C NMR (100.6 MHz, acetone-d,) 6 170.88, 142.40, 138.08,129.57,129.06,128.36,127.72,77.81,73.46,69.82,61.9,40.98,
38.48, 21.05. Cyclization of trans -3-(Hydroxypropoxy)-1-phenyl-1,5hexadiene (54). The diene 54 (2 mmol) was cyclized according to the procedure described for 9. After the mixture was stirred at ambient temperature for 42 h, 10 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (3 X 40 mL l/l).The organic phase was washed with water (20 mL) and saturated aqueous Na2C03 (2 X 20 mL). The combined aqueous phase from the wash was extracted with petroleum ether/EhO (50 mL l/l),and the organic phase was washed with saturated aqueous Na2C03 (2 x 5 mL). After drying of the combined organic phase (MgS04)and removal of the solvent in vacuo, 537.6 mg of a dark oil was obtained. Flash chromatography (a stepwise gradient of petroleum ether/EhO, 2/3 and 1/4, was used) gave 34 (23.5 mg, 0.11 mmol),35 (100 mg, 0.365 mmol),and a mixture of 66a/66b (263 mg, 0.91 mmol). Yield of 66a/66b, 46%; ratio, 55/45. The two diastereomers were separated by HPLC (petroleum ether/EtOAc, 3/2) for structural determination. 66a: Rf = 0.1 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.18-7.42 (m, 5 H, Ph) 6.57 (br s, wl/2 = 6 Hz, 1H, PhCH=C), 5.30 (m, 1 H, CHOAc), 4.58 (br s, wl/,= 12 Hz, 1 H, CHO), 3.47-3.74 (m, 4 H, OCH2CH,CH20H), 3.04 (br dd, J = 17 and 7 Hz, 1 H, C=CCH,), 2.50 (br dd, J = 17 and 4 Hz, 1 H, C= CCHz), 2.30-2.44 (ddd, part of AB, J = 14.5, 6, and 3 Hz, 1 H, CH(OAc)CH,CHO), 1.93-2.09 (m, 1 H, CH(OAc)CH,CHO), 2.02 (s,3 H, OAc), 1.72-1.90 (m, 3 H, CH2CH2CH2and OH); '3c NMR
J. Org. Chem., Vol. 54, No. 20, 1989 4927 (100.6 MHz) 6 170.&36,140.60,137.07,128.47,128.30,128.14,127.03, 77.21, 73.33, 66.00, 61.26, 39.66, 38.74, 32.35, 21.22. 66b: R, = 0.1 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.17-7.38 (m, 5 H, Ph), 6.55 (br s, wl/,= 6 Hz, 1 H, PhCH=C), 5.18 (m, 1H, CH(OAc)),4.41 (br d, J = 5 Hz, 1 H, CHO), 3.73 (q, J = 5.5 Hz, 2 H, CHZOH), 3.60 (t,J = 5.5 Hz, 2 H, OCH&H&HZOH), 2.88 (ddd, part of AB, J = 17.5, 6.5, and 2 Hz, 1 H, C=CCH2), 2.79 (br d, part of AB, J = 17.5 Hz, 1H, C=CCH2),2.39 (t, 1H, OH), 2.0-2.28 (m, 2 H, CH(OAc)CH2CHO),2.07 ( 8 , 3 H, OAc), 1.72-1.93 (m, 2 H, OCH,CH2CHzO); 13C NMR (100.6 MHz) 6 171.12, 141.08, 137.10, 128.46, 128.29 (2 C), 127.09, 77.48,73.18, 67.09, 62.14, 40.07, 38.03, 32.19, 21.21. Cyclization of trans -3-(4-Hydroxybutoxy)-l-phenyl1,5hexadiene (55). Compound 55 (2 mmol) was cyclized according to the procedure described for 9. After the mixture was stirred for 52 h at ambient temperature, the reaction mixture was worked up in the same way as described for 54 to give 625.2 mg of a dark oil. Flash chromatography (a stepwise gradient of petroleum ether/EhO, 3/2,1/1,2/3,1/9, was used) gave 38.9 mg (0.18mmol) of 34, 109.6 mg (0.4 mmol) of 35, and 255 mg (0.84 mmol, 42%) of 67a/67b in a ratio of 55/45. 67a: R, = 0.08 (petroleum ether/EhO, 2/3); 'H NMR (400 MHz, peaks assigned from a mixture of 67a/67b) 6 7.2-7.4 (m, 5,H, Ph), 6.56 (br s, 1 H, PhCH=C), 5.31 (m, 1H, CH(OAc)),4.54 (m, 1H, CHO), 3.38-3.67 (m, 4 H, OCH2CH2CH2CH,0H),3.06 (br dd, J = 17 and 7 Hz, 1 H, C= CCH2),2.49 (br dd, J = 17 and 4 Hz, 1H, C=CCH2),2.36 (ddd, J = 14.5,6 and 3 Hz,1H, CH(OAc)CH,CHO), ca. 2.15 (1H, OH), 2.01 (s,3 H, OAC),1.99 (dt, J = 14.5 and 6 Hz, 1 H, CH(0Ac)CH,CHO), 1.561.74 (m, 4 H, OCHz, CH2CHzCHzOH);13CNMR (100.6 MHz, peaks assigned from a mixture of 67a/67b) 6 171.07 (s, 1 C), 140.65 (s, 1 C), 136.94 (s, 1 C), 128.1-128.5 (d, 2 C, overlapping peaks), 127.99 (d, 1 C), 126.86 (d, 1 C), 77.05 (d, 1 C), 73.33 (d, 1C), 67.40 (t, 1C), 62.47 (t, 1C), 39.60 (t, 1C), 38.71 (t, 1 C), 29.83 (t, 1 C), 26.56 (t, 1 C), 21.13 (4, 1 C). 67b: R/ = 0.08 (petroleum ether/EhO, 2/31; 'H NMR (400 MHz, peaks assigned from a mixture of 67a/67b) 6 7.2-7.4 (m, 5 H, Ph), 6.56 (br s, 1 H, PhCH=C), 5.13 (m, 1 H, CH(OAc)), 4.42 (m, 1 H, CHO), 3.38-3.67 (m, 4 H, OCH2CH2CH20H),2.86 (ddd, part of AB, J = 17,6.5 and 2 Hz, 1H, C=CCH2),2.80 (br d, part of AB, J = 17 Hz, 1 H, C=CCH2), 2.1-2.2 (m, 3 H, CH(OAc)CH,CHO and OH), 2.06 ( 8 , 3 H, OAc), 1.56-1.74 (m, 4 H, OCH,CH,CH,CH20H); 13C NMR (100.6 MHz, peaks assigned from a mixture of 67a/67b) 6 170.80 (s, 1C) 140.82 (s, 1C), 137.03 (s, 1 C), 128.24 (d, 1C), 128.2-128.5 (d, 2 C, overlapping peaks), 126.94 (d, 1C), 77.09 (d, 1C), 72.91 (d, 1C), 67.49 (t, 1C), 62.41 (t, 1 C), 40.07 (t, 1 C), 37.78 (t, 1 C), 30.00 (t, 1C), 26.68 (t, 1 C), 21.18 (4, 1 C). Cyclization of trans -3-(2-Cyanoethoxy)-l-phenyl-1,5hexadiene (59). Compound 59 (2 mmol) was treated in the same way as 9. After the mixture was stirred at ambient temperature for 30.5 h, 5 mL of brine was added and the aqueous phase was extracted with petroleum ether/EhO (3 X 40 mL l/l). The combined organic phase was washed with water (20 mL) and saturated aqueous NaZCO3(2 X 20 mL). The aqueous phase from the wash was then extracted with petroleum ether/EhO (30 mL l / l ) , and the organic phase was washed with aqueous saturated Na2C03(5 mL). After drying (MgSOJ of the combined organic phase and removal of the solvent in vacuo, 532 mg of an oil was obtained. Following flash chromatography (a stepwise gradient of petroleum ether/EhO, 3/2,2/3, and 1/4, was used), 34 (13 mg, 0.06 mmol), 35 (84 mg, 0.306 mmol), and one fraction containing a mixture of 68a and 68b (287 mg,1.0 mmol) and one other isomer (43 mg, 0.151 mmol) were obtained. Yield of 68a/68b, 50%; ratio, 60/40. 68a: Rf = 0.22 (petroleum ether/EhO, 2/3); 'H NMR (400 MHz, peaks assigned from a mixture of 68a/68b) 6 7.2-7.4 (m, 5 H, Ph), 6.61 (br s, 1H, PhCH=C), 5.32 (m, 1 H, CHOAc), 4.63 (m, 1 H, CHO), 3.5-3.6 (m, 2 H, OCH2CH2CN),3.06 (br dd, J = 17 and 7 Hz,1H, C=.CCH&,2.49 (t,J = 6.3 Hz,2 H, CHZCN), 2.45-2.53 (m, 1 H, C=CCH2), 2.36 ( d d d , J = 14.5, 6, and 3 Hz, 1 H, CH(OAc)CH,CHO),2.02 (s, 3 H, OAc), 1.95-2.05 (m, 1H, CH(OAc)CH,CHO); 13CNMR (100.6 MHz; peaks assigned from a mixture of 68a/68b) 6 170.69 (s, 1 C), 139.76 ( 8 , 1 C), 136.75 (s, 1C), 128.2-128.4 (d, 3 C, overlapping peaks), 127.09 (d, 1 C), 117.78 (s, 1 C), 77.3 (d, 1C), 73.02 (d, 1 C), 62.12 (t, 1C), 39.25 (t, 1 C), 38.57 (t, 1 C), 21.05 (9, 1C), 18.81 (t, 1 C). 68b: R, = 0.22 (petroleum ether/EhO, 2/3); 'H NMR (400 MHz, peaks
4928
J. Org. Chem., Vol. 54, No. 20,1989
assigned from a mixture of 68a/68b) 6 7.2-7.4 (m, 5 H, Ph), 6.61 (br s, 1 H, PhCH=C), 5.15 (m, 1 H, CH(OAc)), 4.50 (m, 1 H, CHO), 3.55-3.65 (m, 2 H, OCH2CH2CN),2.88 (ddd, part of AB, J = 17,6.5, and 2 Hz, 1 H, C=CCHz), 2.79 (br d, part of AB, J = 17 Hz, 1 H, C=CCHz), 2.55 (t, J = 6.2 Hz, 2 H, CHZCN), 2.1-2.24 (m, 2 H, CH(OAc)CH2CHO),2.07 (s,3 H, OAc); '% N M R (100.6 MHz, peaks assigned from a mixture of 68a/68b) 6 170.98 (9, 1 C), 139.96 (8, 1 C), 136.65 (9, 1 C), 128.2-128.4 (d, 3 C, overlapping peaks), 127.16 (d, 1C), 117.70 (s, 1 C), 77.3 (d, 1C), 72.57 (d, 1 C), 62.08 (t, 1 C), 39.83 (t, 1 C), 37.69 (t, 1 C), 21.14 (q, 1 C), 18.92 (t, 1 C). Cyclization of trans -3-(3-Cyanopropoxy)-l-phenyl-1,5hexadiene (60). Compound 60 was cyclized using the procedure described for 9 and worked up in the same way as 59 to yield 564.9 mg of an oil. Following flash chromatography (same gradient as for 59) one fraction containing a mixture of 60 (63.5 mg, 0.263 mmol), 34 (19.7 mg, 0.09 mmol), and 35 (55.8 mg, 0.203 mmol) and another fraction containing a mixture of 69a,b (260 mg, 0.87 mmol) together with another isomer (33 mg, 0.11 mmol) were afforded. Yield of 69a/69b, 44%; ratio, 58/42. The two diastereomers were partially separated on HPLC (petroleum ether/EtOAc, 7/3). 69a: R, = 0.26 (petroleum ether/EhO, 2/3); 'H NMR (200 MHz) 6 7.2-7.42 (m, 5 H, Ph), 6.57 (br s, w1/,= 6 Hz, 1H, PhCH==C), 5.3 (m, 1H, CH(OAc)),4.64 (m, 1H, CHO), 3.38-3.6 (m, 2 H, OCH,CH,), 3.04 (br dd, J = 17 and 6.5 Hz, 1 H, C=CCH,), 2.50 (br dd, J = 17 and 4 Hz, 1 H, C=CCH2), 2.25-2.4 (m, 1 H, CH(OAc)CH2CHO),2.32 (t, J = 7 Hz, 2 H, CH,CN), 2.03 (s, 3 H, OAc), 1.95-2.1 (m, 1H, CH(OAc)CH2CHO), 1.87-1.93 (m, 2 H, CH,CH,CH,CN); 13C NMR (100.6 MHz) 6 170.81,140.44,137.03,128.42,128.34,128.17,127.13,119.42,77.14, 73.19, 64.73, 39.66, 38.68, 25.94, 21.21, 14.11. 69b: Rf = 0.26 (petroleum ether/EhO, 2/3); 'H NMR (200 M H z ) 6 7.17-7.42 (m, 5 H, Ph), 6.57 (br s, wl/,= 6 Hz, 1H, PhCH=C), 5.16 (apparent quintet, 1 H, CHOAc), 4.49 (m, 1 H, CHO), 3.44-3.64 (m, 2 H, OCH2CH2),2.89 (ddd, part of AB, J = 17, 6.5, and 2 Hz, 1 H, C=CCH2), 2.78 (br d, part of AB, J = 17 Hz, 1H, C===CCH),2.42 (t, J = 6.5 Hz, 2 H, CH,CN), 2.14-2.22 (m, 2 H, CH(0Ac)CH2CHO),2.07 (s,3 H, OAc), 1.84-2.0 (m, 2 H, CH,CHzCH2CN); 13C NMR (100.6 MHz) 6 170.92, 140.62, 136.92, 128.37 (2 C), 127.22,126.59,119.45,77.15,72.83,64.49,40.19,37.78,26.03,21.28, 14.12. Anal. Calcd for (mixture of 69a/69b) C1&1NO3: C, 72.22; H, 7.07; N, 4.68. Found: C, 72.16; H, 7.08; N, 4.59. Cyclization of trans -344-Cyanobutoxy)-1-phenyl-1,5hexadiene (61). Compound 61 (2.75 mmol) was treated in the same way as 60. Workup yielded 815.3 mg of a dark oil. Flash chromatography (a stepwise gradient of petroleum ether/EkO, 7/3,3/2,1/1, and 2/3, was used) gave 47 mg (0.22 mmol) of 34, 112 mg (0.41 mmol) of 35, and 397 mg (1.27 mmol, 46%) of 70a/70b in a ratio of 59/41. 70a: R, = 0.16 (petroleum ether/ Et,O, l / l ) ; 'H NMR (400 MHz, peaks assigned from a mixture of 70a/70b) 6 7.2-7.4 (m, 5 H, Ph), 6.57 (br s, 1 H, PhCH=C), 5.30 (m, 1 H, CHOAc), 4.58 (m, 1 H, CHO), 3.34-3.51 (m, 2 H, OCH,, 3.05 (br dd, J = 17 and 7 Hz, 1H, C==CCHJ, 2.50 (br dd, J = 17 and 4 Hz, 1 H, C=CCH2), 2.25-2.35 (m, 1 H, hidden by CHzCN in the two diastereomers, CH(OAc)CH&HO), 2.25-2.3 (m, 2 H, CH,CN), 2.02 (s, 3 H, OAc), 1.97-2.05 (m, 1 H, CH(OAc)CH2CHO),1.63-1.7 (m, 4 H, OCH,CH&H2); 13C NMR (100.6 MHz, peaks assigned from a mixture of 70a/70b) 6 170.77 (8, 1 C), 140.65 ( 8 , 1 C), 137.05 (s, 1 C), 128.1-128.4 (d, 2 C, overlapping peaks), 127.93 (d, 1 C), 126.95 (d, 1 C), 119.51 (s, 1 C), 76.96 (d, 1 C), 73.23 (d, 1C), 66.31 (t, 1C), 39.58 (t, 1C), 38.64 (t, 1C), 28.77 (t,1C), 22.47 (t, 1C), 21.13 (q, 1 C), 16.86 (t, 1 C). 70b R, = 0.16 (petroleum ether/EhO, 1/11; 'H NMR (400 MHz, peaks assigned from a mixture of 70a/70b) 6 7.2-7.4 (m, 5 H, Ph), 6.57 (br s, 1H, PhCH=C), 5.14 (m, 1 H, CHOAc), 4.43 (m, 1H, CHO), 3.34-3.51 (m, 2 H, OCH2), 2.87 (ddd, part of AB, J = 17, 6.5, and 2 Hz, 1H, C=CCH,), 2.78 (br d, part of AB, J = 17 Hz, 1 H, C=CCH2), 2.3-2.35 (m, 2 H, CHzCN), 1.99-2.22 (m, 2 H, CH(OAc)CH,CHO), 2.06 (s, 3 H, OAc), 1.7-1.75 (m, 4 H, OCH,CH2CH,); 13C NMR (100.6 MHz, peaks assigned from a mixture of 70a/70b 6 170.92 (s, 1 C), 140.79 (s, 1 C), 136.93 (s, 1C), 128.1-128.4 (d, 2 C, overlapping peaks), 128.15 (d, 1C), 127.03 (d, 1 C), 119.51 (s, 1 C), 76.92 (d, 1 C), 72.83 (d, 1 C), 66.24 (t, 1 C), 40.10 (t, 1 C), 37.75 (t, 1 C), 28.82 (t, 1 C), 22.67 (t, 1 C), 21.21 (q, 1 C), 16.88 (t, 1 C).
Antonsson et al. Cyclization of trans -3-(Carboxymethoxy)-l-phenyl-1,5hexadiene (62). The diene 62 (2 mmol) was cyclized using the procedure described for 9. After the mixture was stirred for 70 h a t ambient temperature, 10 mL of brine was added, and the aqueous phase was extracted with petroleum ether/EhO (2 X 30 mL 7/3, and 20 mL l/l). The organic phase was washed with 7 X 5 mL of HzO and extracted with saturated Na2C03(2 X 20 mL). The carbonate phase was acidified by the addition of 2 M HCl(50 mL) and extracted with EhO (3 X 30 mL). After drying (MgSO,) of the combined organic phase. and removal of the solvent in vacuo, 230.3 mg (0.79 mmol, 40%) of 71a/71b in a ratio of 70/30 was obtained. The organic phase obtained after the extraction with Na2C03was dried (MgS04),and the solvent was removed. Flash chromatography (petroleum ether/EhO, 7/3) yielded 34.2 mg (0.158 mmol) of 34 and 92.3 mg (0.337 mmol) of 35. 71a: 'H NMR (400 MHz, peaks assigned from a mixture of 71a/71b) 6 7.2-7.45 (m, 5 H, Ph), 6.66 (br s, w l p = 6 Hz, 1 H, PhCH=C), 5.3-5.37 (m, 1 H, CHOAc), 4.87 (m, 1 H, CHO), 3.99 (8, 2 H, CH,COOH), 3.09 (br dd, J = 17 and 7 Hz, 1 H, C==CCHz), 2.51 (br dd, J = 17 and 4 Hz, 1H, W C H J , 2.38 (ddd, J = 15,6 and 3 Hz, 1 H, CH(OAc)CH,CHO), 2.04 (s, 3 H, OAc), 2.21 (m, 1H, CH(OAc)CH,CHO); I3C NMR (100.6 MHz, peaks assigned from a mixture of 71a/71b) 6 174.50 (9, 1 C), 170.97 (s, 1 C), 139.33 (s, 1 C), 136.61 ( 8 , 1 C), 128.3-128.5 (d, 3 C, overlapping peaks), 127.18 (d, 1C), 77.46 (d, 1C), 73.13 (d, 1C), 64.38 (t, 1 C), 39.21 (t, 1 C), 38.71 (t, 1C), 21.07 (q, 1 C). 71b: 'H NMR (400 MHz, peaks assigned from a mixture of 71a/71b 6 7.2-7.45 (m, 5 H, Ph), 6.66 (br s, wllz = 6 Hz, 1 H, PhCH=C), 5.28-5.35 (m, 1 H, CHOAc), 4.77 (br d, J = 5 Hz, 1 H, CHO), 4.15 (A part of AB, JAB = 16.3 Hz, 1H, CHZCOOH),4.01 (Bpart of AB, JAB= 16.3 Hz, 1 H, CH2COOH), 2.95 (ddd, part of AB, J = 17.5, 7, and 2 Hz, 1 H, C==CCH2),2.82 (br d, part of AB, J = 17.5, 1 H, C= CCH,), 2.2-2.26 (m, 1H, CH(OAc)CH,CHO), 2.1-2.16 (m, 1 H, CH(OAc)CH,CHO), 2.08 (6,3 H, OAc); 13C NMR (100.6 MHz, peaks assigned from a mixture of 71a/71b) 6 173.70 (s, 1C), 170.97 (9, 1 C), 139.3 (9, 1 C), 136.44 (9, 1 C), 128.3-128.5 (d, 3 C, overlapping peaks), 127.35 (d, 1C), 77.76 (d, 1 C), 72.99 (d, 1C), 64.41 (t, 1 C), 39.75 (t, 1 C), 37.94 (t, 1 C), 21.07 (q, 1 c). Cyclization of trans -3-(2-Carboxyethoxy)-l-phenyl-1,5hexadiene (63). Cyclization of 63 (1mmol) and workup according to the procedure described for 62 afforded 10.8 mg (0.05 mmol) of 34, 43.2 mg (0.158 mmol) of 35, and 130.5 (0.43 mmol, 43%) of 72a/72b in a ratio of 63/37. 72a: 'H NMR (400 MHz, peaks assigned for a mixture of 72a/72b) 6 7.2-7.45 (m, 5 H, Ph), 6.58 (br s, 1H, PhCH=C), 5.31 (m, 1H, CHOAc), 4.57 (m, 1H, CHO), 3.68 (t, J = 6.1 Hz, 2 H, OCH2CH2COOH),3.06 (br dd, J = 17 and 7 Hz, 1H, C=CCH2),2.60 (t,J = 6.1 Hz, 2 H, CH&OOH), 2.48 (br dd, J = 17 and 4 Hz, 1H, C=CCH2), 2.41 (ddd, J = 14.5, 6, and 3 Hz,1H, CH(OAc)CH,CHO),2.02 (s,3H, OAc), 1.95-2.04 (m, 1 H, CH(OAc)CH2CHO);13C NMR (100.6 MHz, peaks assigned from a mixture of 72a/72b) 6 177.22 (s, 1 C), 171.01 (s, 1C), 140.26 (s, 1C), 136.87 (s, 1C), 128.2-128.5 (d, 3 C, overlapping peaks), 126.97 (d, 1 C), 77.17 (d, 1 C), 73.36 (d, 1 C), 62.26 (t, 1 C), 39.59 (t, 1C), 38.45 (t, 1C), 34.81 (t, 1C), 21.13 (q, 1C). 72b: 'H NMR (400 MHz, peaks assigned from a mixture of 72a/72b) 6 7.2-7.45 (m, 5 H, Ph), 6.60 (br s, 1 H, PhCH=C), 5.17 (m, 1 H, CHOAc), 4.49 (m, 1 H, CHO), 3.71 (t, J = 6.0 Hz, 2 H, OCH,CH,COOH), 2.88 (ddd, part of AB, J = 17.6 and 2 Hz, 1 H, C==CCH2),2.80 (br d, part of AB, J = 17 Hz, 1 H, CSCCH,), 2.65 (t,J = 6.0, 2 H, CH,COOH), 2.11-2.26 (m, 2 H, CH(0Ac)CH,CHO), 2.06 (s, 3 H, OAc); 13C NMR (100.6 MHz, peaks assigned from a mixture of 72a/72b) 6 177.05 (9, 1 C), 171.28 (s, 1C), 140.29 (s, 1C), 136.76 (s, 1C), 128.2-128.5 (d, 3 C, overlapping peaks), 127.07 (d, 1C), 77.24 (d, 1 C), 72.94 (d, 1C), 62.26 (t, 1 C), 40.00 (t, 1 C), 37.58 (t, 1 C), 34.87 (t, 1 C), 21.13 (q, 1 c). Cyclization of trans -3-(3-Carboxypropoxy)-l-phenyl-1,5hexadiene (64). Cyclization of 64 (1.9 mmol) and workup according to the procedure described for 62 afforded 28.7 mg (0.133 mmol) of 34, 104.2 mg (0.38 mmol) of 35, and 281 mg (0.87 mmol, 46%) of 73a/73b in a ratio of 60/40. 73a: 'H NMR (400 MHz, peaks assigned from a mixture of 73a/73b) 6 7.2-7.4 (m, 5 H, Ph), 6.55 (br s, w1p = 6 Hz, 1H, PhCH=C), 5.30 (m, 1 H, CHOAc), 4.54 (m, 1 H, CHO), 3.45-3.51 (m, 2 H, OCH,),3.06 (br dd, J = 17 and 6.5 Hz,1H, C==C!CH,), 2.45-2.53 (m, 1H, M C H J , 2.33 (ddd, J = 14.6 and 3 Hz, 1H, CH(OAc)CH,CHO), 2.39 (m, 2 H, CH,CHO), 2.01 (s, 3 H, OAc), 1.95-2.0 (m, 1 H, CH(0Ac)-
J. Org. Chem.
1989,54, 4929-4935
CH,CHO), 1.86 (m, 2 H, OCH,CH,); 13CNMR (100.6 MHz, peaks assigned from a mixture of 73a/73b) 6 179.17 (s, 1C), 170.89 (s, 1C), 140.57 (s,1 C), 136.92 (s, 1C), 127.9-128.4 (d, 3 C, overlapping peaks), 126.86 (d, 1 C), 76.89 (d, 1 C), 73.33 (d, 1 C), 66.08 (t, 1 C), 39.56 (t,1C), 38.62 (t, 1C), 30.64 (t, 1C), 24.82 (t, 1 C), 21.05 (q,1 C). 73b lH NMR (400 MHz, peaks assigned from a mixture of 73a/73b) 6 7.2-7.4 (m, 5 H, Ph), 6.55 (br s, w1 = 6 Hz, 1H, PhCH=C), 5.14 (m, 1H, CH(OAc)),4.40 (m, 1H, dHO), 3.37-3.43 (m, 2 H, OCH,), 2.88 (ddd, part of AB, J = 17,6.5, and 2 Hz, 1 H, C=CCH2), 2.81 (br d, part of AB, J = 17 Hz, 1H, C=CCH2), 2.45-2.51 (m,2 H, CH,COOH), 2.1-2.2 (m, 2 H, CH(0Ac)CH,CHO), 2.06 (s, 3 H, OAc), 1.92 (m, 2 H, OCHzCHz);13CNMR (100.6 MHz, peaks assigned from a mixture of 73a/73b) 6 179.17 (s, 1C), 171.16 (s, 1C), 140.74 ( s , l C), 136.84 ( s , l C), 127.9-128.4
4929
(d, 3 C, overlapping peaks), 126.96 (d, 1 C), 76.95 (d, 1 c ) , 72.97 (d, 1 C), 65.93 (t, 1 C), 39.99 (t, 1 C), 37.62 (t, 1 C), 30.69 (t, 1 C), 24.82 (t, 1 C), 21.10 (q, 1 C).
Acknowledgment. This work was supported by the Swedish Natural Science Research Council and by the Centre National de la Recherche Scientifique (Convention d'Bchange). The NOE experiments were kindley performed by Dr. Ulla Jacobsson. Supplementary Material Available: 'H NMR spectra of compounds for which elemental analyses are lacking (74 pages). Ordering information is given on any current masthead page.
Photoreactions of N-Methylphenanthrene-9,lO-dicarboximide with Alkenes and Dienes. Heavy-Atom Effect of Halides Yasuo Kubo,* Soshi Togawa, Kengo Yamane, Akio Takuwa, and Takeo Araki Department of Chemistry, Faculty of Science, Shimane University, Matsue, Shimane 690, Japan Received February 28, 1989
Photoreaction (>400 nm) of N-methylphenanthrene-9,lO-dicarboximide(1) in benzene gave the dimer syn-2. Photoreaction (>400 nm) of 1 with alkenes and dienes 3 in benzene gave 2, products 4 of insertion of the double bond of 3 into the C-N bond of 1, and cyclobutanes 5 and 7. Irradiation of 2, 4a, 4m,n, and 5a at a shorter wavelength (>320 nm) gave, respectively, 1, decarbonylation product 6, intramolecular cycloadducts 8m,n, and 1 + 3a. In the photoreaction of 1 with 3b, addition of methyl iodide to benzene (1:lv/v) suppressed the dimerization and insertion reactions, and only cyclobutanes 5b and 7b were formed. Methyl iodide and iodobenzene were equally effective in increasing the ratio (5b + 7b)/4b with increasing halide concentration; butyl bromide and bromobenzene were less effective. The ratio 5:7 was independent of the concentration of methyl iodide. Dilution plots of insertion and cyclobutane formation in the photoreaction of 1 with 3b showed that methyl iodide quenched the excited state of 1 which led to insertion. The results indicate that the syn dimerization and the insertion occurred from the singlet excited state of 1, and the cyclobutane arose mainly from the triplet excited state. The activity of the halides in these photoreactions is attributed to the heavy-atom effect.
Introduction Photochemistry of phthalimides in the presence of alkenes has been the subject of many investigations.' Several types of reactions have been observed, including alcohol addition (electron-transfer reaction)? insertion of the alkene into the imide moiety? oxetane formation$ and (1) Coyle, J. D. Synthetic Organic Photochemistry; Horspool, W. M., Ed.; Plenum: New York, 1984; p 259. Mazzocchi, P. H. Organic Photochemistry; Padwa, A., Ed.; Marcel Dekker: New York, 1981; Vol. 5, p 421. Kanaoka, Y. Acc. Chem. Res. 1978, 11,407. (2) Maruyama, K.; Kubo, Y.; Machida, M.; Oda, K.; Kanaoka, Y.; Fukuyama, K. J. Org. Chem. 1978,43, 2303. Maruyama, K.; Kubo, Y. Chem. Lett. 1978,851. Mazzocchi, P. H.; Minamikawa, S.; Wilson, P. Tetrahedron Lett. 1978,4361. Maruyama, K.; Kubo, Y. J.Am. Chem. SOC. 1978,100, 7772. Machida, M.; Oda, K.; Maruyama, K.; Kubo, Y.; Kanaoka, Y. Heterocycles 1980,14,779. Mazzocchi, P. H.; Khachik, F. Tetrahedron Lett. 1981,4189. Maruyama, K.; Kubo, Y. J. Org. Chem. 1981,46,3612. Maruyama, K.; Kubo, Y. Ibid. 1986,50,1426. Mazzocchi, P. H.; Minamikawa, S.; Wilson, P. Ibid. 1986,50, 2681. (3) (a) Mazzocchi, P. H.; Bowen, M.; Narian, N. J. Am. Chem. SOC. 1977,99,7063. (b) Mazmchi, P. H.; Minamikawa, S.; Bowen, M. J. O g . Chem. 1978,43,3079. (c) Maruyama, K.; Kubo, Y. Chem. Lett. 1978,769. (d) Kanaoka, Y.; Yoshida, K.; Hatanaka, Y. J. Org. Chem. 1979,44,664. (e) Mazzocchi, P. H.; Minamikawa, S.; Wilson, P. Ibid. 1979,44,1186. (0 Mazzocchi, P. H.; Minamikawa, S.; Wilson, P.; Bowen, M.; Narian, N. Ibid. 1981,46,4846. (g) Mezzocchi, P. H.; Khachik, F.; Wilson, P.; Highet, R. J. Am. Chem. SOC. 1981,103,6498. (h) Mazzocchi, P. H.; Wilson, P.; Khachik, F.; Klingler, L.; Minamikawa, S. J. Org. Chem. 1983,48,2981. (i) Maruyama, K.; Ogawa, T.; Kubo, Y.; Araki, T. J.Chem. SOC.,Perkin Tram. 1 1985, 2025. (i)Suarez, R. S.; Segura, R. G. Tetrahedron Lett.
photored~ction.~The effect of arene structure on the photochemistry of arenedicarboximides has been investigated.6.7 We have studied the effect of an extended ?r-conjugation system and have reported photoreactions in which the arene structure plays a crucial role in determining the reaction p a t h ~ a y .Thus ~ the predominant reactions of N-methylnaphthalene-1,8-, -2,3-, and -1,2dicarboximides with alkenes are cyclobutane formation? oxetane formation,7dand insertion of the alkene into the imide bond,7brespectively. Here we report on the photoreactions of N-methylphenanthrene-9,lO-dicarboximide(1) with alkenes dienes and on the heavy-atom effect on these reactions. Internal (4) (a) Mazzocchi, P. H.; Minamikawa, S.; Bowen, M. Heterocycles 1978,9,1713. (b) Machida, M.; Takechi, H.; Kanaoka, Y. Tetrahedron Lett. 1982, 23, 4981. (c) Mazzocchi, P. H.; Klingler, L.; Edwards, M.; Wilson, P.; Shook, D. Ibid. 1983, 143. (5) (a) Kanaoka, Y.; Hatanaka, Y. Chem. Pharm. Bull. 1974,22,2205. (b) Mazzocchi, P. H.; Khachik, F. Tetrahedron Lett. 1983, 1879. (c) Mazzocchi, P. H.; Klinger, L. J. Am. Chem. SOC. 1984,106,7567. (6) Mazzocchi, P. H.; Somich, C.; Ammon, H. L. Tetrahedron Lett. 1984,3551. Somich, C.; Mazzocchi, P. H.; Ammon, H. L. J. Org. Chem. 1987,52,3614. (7) (a) Kubo, Y.; Tojo, S.; Suto, M.; Toda, R.; Araki, T. Chem. Lett. 1984,2075. (b) Kubo, Y.; Toda, R.; Yamane, K.; Araki, T. Bull. Chem. SOC. Jpn. 1986, 59, 191. (c) Kubo, Y.; Suto, M.; Tojo, S.; Araki, T. J. Chem. SOC.,Perkin Trans. 1 1986, 771. (d) Kubo, Y.; S u b , M.; Araki,
T.; Mazzocchi, P. H.; Klingler, L.; Shook, D. Somich, C. J. Org. Chen). 1986,51,4404.
1988,29,1071.
0022-3263/89/1954-4929$01.50/0
0 1989 American Chemical Society
